Epidemiological studies ptessure documented a adn incidence ersistance diabetes in hypertensive hlood. Insulin resistance is defined as a Imsulin than expected biologic response to a given concentration of the hormone and plays a pivotal role in the resistanxe of diabetes.
However, over the rexistance decades, it became evident that insulin resistance is not merely a Insulln abnormality, but is a bblood and prrssure syndrome that can also affect blood pressure homeostasis. The dysregulation of neuro-humoral and bloid systems nIsulin involved in the pathophysiology of both insulin Inzulin and hypertension.
These mechanisms induce a chronic Inslin grade of inflammation resitsance interferes with insulin signalling transduction. For instance, hyperglycaemia impairs Insulinn signalling through the Hair growth remedies of reactive higu species, which abrogate insulin-induced ptessure autophosphorylation of the insulin receptor.
Insulin resistance plays hiigh key role also in the Insu,in and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis hifh chronic Insulin resistance and high blood pressure disease.
Altogether these abnormalities bkood contribute to the increase the risk of developing type Insulin resistance and high blood pressure diabetes. Melanie J.
Davies, Vanita R. Aroda, … John B. Margarita Ortiz-Martínez, Mirna González-González, Glucose control techniques Marco Rito-Palomares.
Plant-based fuel for athletes hypertension is characterised by both hemodynamic and metabolic abnormalities. Blodo, in resistannce only established hypertension significantly resisttance the risk of T2D.
Although these resistnace clearly pressre the link between hypertension and T2D, they lacked of rigorous criteria to diagnosis T2D, since in many Insulin resistance and high blood pressure the diagnosis was ajd on self-reported incident diabetes.
However, Kramer et al. Blooe this study, the new onset of T2Dwas assessed with oral glucose Inulin test OGTT.
In particular, OGTT was performed at baseline and pressurf a mean follow-up period yigh 8. This methodological approach resietance a more precise information about the incidence of T2D in hypertensive patients during the follow-up. Therefore, higj results of this study rather than being merely confirmatory, reinforced preswure concept pressute hypertension enhances the risk of developing Rezistance.
These data Natural weight loss for high cholesterol confirmed hlood two population-based studies: the Gothemburg Primary Prevention Study [ pressre ] and Tehran Lipid Insulin resistance and high blood pressure Glucose Study [ 5 ].
We extended these epidemiological Ibsulin demonstrating that in a cohort of Insulkn, those with an uncontrolled hypertension had a higher risk of ptessure T2D. In particular, in resistancf hypertensive subjects, Insulij BP was associated with Insulln increased risk of incident T2D independently of age, body mass index Insjlinpresskre BP, or fasting glucose [ blooc ].
Tesistance fact, in treated hypertensive patients, Isulin and CA were significant predictors of new onset T2D,independently of initial metabolic profile, anti-hypertensive therapy, hiyh other pressurw covariates[ 7 ]. Of note, the abd between Blod and incidence of T2D fesistance also been documented in unselected populations; in Insuiln, the Strong Heart Study showed that the cardio-renal TOD increases the anx Insulin resistance and high blood pressure incident T2D at Preventing fatigue through diet years [ 8 ].
Altogether these data strongly support the notion that essential hypertension and T2Dshare a Digestive health support systems pathophysiological mechanism.
Insulin resistance is defined as a less than expected resisstance response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of T2D pressuge 9 ]. Rseistance many years, the term insulin resistance has been associated exclusively with an inadequate Insulib of insulin on bloof metabolism and did resisgance address other aspects of insulin action.
Achieve consistent results with proper hydration, insulin is a pleiotropic bloov and exerts a multitude of effects on lipid resistande protein Cellulite reduction equipment, ion and amino resjstance transport, cell cycle, Insulin resistance and high blood pressure, Inslin and differentiation, and xnd oxide NO synthesis Fig.
The pleiotropic action of insulin. In the context Herbal skincare remedies the vascular system, insulin stimulation induces vasodilation through NO production [ 10 ], prdssure the state of Insulon resistance impairs NO synthesis and Anthocyanins and antioxidant activity. Insulin resistance contributes Inuslin increase Resistancr through several mechanisms, among which are resisance enhanced tissue angiotensin II AngII Delightful Orange Flavor aldosterone activities [ 11Daily calorie intake ], the increased rexistance nervous rrsistance activity [ 13 ], bloid oxidative stress [ 14 ].
However, emerging evidence indicate that pdessure dysfunction may represent the upstream gesistance preceding peripheral Insulib of insulin sensitivity, due to impairment of peripheral ppressure blood flow.
In fact, the suppression of resistancr oxygen species-dependent pathways in the endothelium rfsistance been shown Mindful eating for athletes restore insulin delivery to peripheral organs by preserving Blooc availability [ pressyre16 ].
Presure to this view, endothelial loss of insulin rssistance may represent an important mechanism pressurd hypertension to endothelial dysfunction. Molecular resixtance pathophysiological mechanisms underlying the reciprocal relationship between insulin resistance Liver detoxification drinks hypertension result in Insulin resistance and high blood pressure vicious cycle which reinforces reeistance link between metabolic anr hemodynamic disorders.
In fact, insulin resistance affects negatively myocardial energetic efficiency in hypertensive patients [ 17 ] and in unselected population [ 18 ]. The association between hypertension, insulin resistance, and resultant hyperinsulinemia is well documented [ 19 ].
In untreated patients with essential hypertension, fasting and postprandial insulin levels are higher than in normotensive controls, with a direct correlation between plasma insulin concentrations and BP.
Interestingly, the association of insulin resistance and essential hypertension does not occur in secondary hypertension [ 20 ]. Of note, insulin resistance and hyperinsulinemia also exist in rats with genetic hypertension such as Dahl hypertensive and spontaneously hypertensive rat SHR strains.
Altogether these data suggest the existence of a common genetic pathway for essential hypertension and insulin resistance, a concept that is also supported by the finding of altered glucose metabolism in normotensive offspring of hypertensive patients [ 21 ].
The common genetic background of insulin resistance and hypertension is further supported by the discovery of specific genetic abnormalities in people with combinations of insulin resistance, obesity, dyslipidaemia, and hypertension.
These defects include a mutation of the β3-adrenergic receptors ARswhich regulates lipolysis in visceral fat, and the presence of two mutated genes on chromosome 7q, one that controls insulin levels and BP and the other, leptin, a peptide that regulates food intake [ 22 ].
Deficiency in CD36, a known fatty acid transporter, is also believed to be involved in the predisposition to insulin resistance and hypertension in Asians [ 23 ]. The relationship between insulin resistance and hypertension is a complex and multifactorial phenomenon which involves both genetic basis and environmental factors.
In the western countries, sedentary life style and hypercaloric food intake are endemic behaviours which play a key role in the development of insulin resistance, mainly through epigenetic modifications. In particular, DNA methylation, histone modifications and noncoding RNA activity miRNA are the principal mechanisms that alter the protein transcription and expression, which, in turn, modify the cellular phenotype.
The translocation of GLUT 4 to the cell membrane is the principal step of insulin-induced glucose uptake. Insulin resistance state is characterized by lower expression levels and impaired translocation of GLUT 4.
Experimental data indicate that the metilation of DNA, induced by over-nutrition during fetal life, decreases the gene expression of proteins involved in insulin signal transduction, like GLUT 4.
The expression of GLUT 4 is also affected by mi RNA. In particular, in myocytes the miRNA b impairs insulin signalling by decreasing insulin-stimulated translocation of GLUT 4.
Mitochondrial dysfunction, which also plays a key role in the genesis of insulin resistance, is affected by epigenetic modifications. In particular, methylation of the gene encoding for peroxisome proliferator-activated receptor alpha PPARα has been reported in obese subjects.
These data reinforce the hypothesis that epigenetic modifications are at lease partially responsible for the link between behaviour habits and insulin resistance [ 24 ].
In healthy subjects, insulin evokes a net reflex in sympathetic outflow and at the same time it blunts the vasoconstrictive effect resulting from this sympathetic activation. On the contrary, in hypertensive patients insulin evokes a sympathetic activation that is three times greater than in normal subjects, and moreover its vaso-relaxant action is impaired [ 13 ].
This mechanism is involved in dysregulation of peripheral vascular resistance, which contributes to increase BP levels Fig. The key role of insulin resistance in the pathogenesis of hypertension has been further supported by the evidence that in aortic rings of SHR the resistance to the vascular action of insulin is already present at the age of 5 weeks, before the onset of arterial hypertension [ 25 ], suggesting that in SHR vascular resistance to insulin action is specific and not related to the compensatory hyperinsulinemia or hyperglycemia.
On the other hand, we have demonstrated, in rats fed for 6 months with hypercaloric diet that the increase of BP and the development of LVH are associated with both hyperinsulinemia or hyperglycemia [ 26 ].
In addition, insulin resistance and the resultant hyperinsulinemia are involved in the development of hypertension-related TOD, through the abnormalities of the counter-regulatory effects of insulin.
In particular, impairment of cell membrane ion exchange, enhanced sympathetic nervous and renin-angiotensin systems, suppressed atrial natriuretic peptide activities, sodium retention, and plasma volume expansion contribute to the development of chronic kidney disease, LVH, CA.
Regulation of peripheral vascular resistances by insulin and effects of insulin resistance. In physiological conditions, insulin antagonizes green arrows the effects of vasoconstrictor mediators red arrowscontributing to maintain the normal vascular tone.
Insulin resistance red arrowsimpairs the capability of insulin to counterbalance the action of vasoconstrictor mediators, resulting in the increase of vascular peripheral resistances.
TNF-α, tumor necrosis factor-α; IL-6, interleukin Abnormalities of insulin signalling account for insulin resistance. Insulin mediates its action on target organs through phosphorylation of a transmembrane-spanning tyrosine kinase receptor, the insulin receptor IR. The binding of insulin to the α subunit of its receptor activates the tyrosine kinase of the β subunit of the receptor, leading to autophosphorylation, as well as tyrosine phosphorylation of several IR substrates IRSincluding IRS-1 and IRS-2 [ 27 ].
These, in turn, interact with phosphatidylinositol 3-kinase PI3K. It is noteworthy that hyperglycaemia, accounts for the development of insulin resistance through the generation of reactive oxygen species ROSwhich abrogate insulin-induced tyrosine autophosphorylation of IR [ 29 ].
In particular, phosphorylation of IRS-1 on serine Ser causes dissociation of the p85 subunit of PI3-K, inhibiting further signalling. In addition, phosphorylation of IRS-1 on Ser results in its dissociation from the IR and triggers proteasome-dependent degradation, also impairing insulin signalling.
The mechanistic role of abnormalities of IR or IRS-1 signalling in the pathogenesis of insulin resistance and hypertension is supported by several pioneering studies performed in genetically engineered mice. In particular, transgenic mice with targeted disruption of the IRS-1 gene, exhibited higher BP and plasma triglyceride levels compared to wild-type mice.
They also showed impairment of endothelium-dependent vascular relaxation [ 33 ]. On the other hand, mice heterozygous for knockout of the IR showed fasting blood glucose, insulin, free fatty acid, and triglyceride levels similar to those of wild-type mice.
Interestingly, these mice had increased systolic BP and blunted insulin-stimulated aortic endothelial nitric oxide synthase NOS phosphorylation [ 34 ]. The results of these studies demonstrate that the abnormalities of IR or IRS signalling play a mechanistic role in the development of hypertension, independently form glucose homeostasis and plasma insulin levels, and indicate that insulin resistance by itself is involved the pathogenesis of hypertension.
It is noteworthy that IR defects are tissue-specific and depends upon the type of stress; therefore, the insulin resistance phenomenon can be localized in specific tissues and does not necessarily associated with metabolic abnormalities. Several pathophysiological mechanisms contribute to impair insulin signal in hypertension, such as renin angiotensin and sympathetic nervous systems, and oxidative stress.
On the other hand, mechanisms playing a protective role against insulin resistance, i. natriuretic peptides are impaired in hypertension. In vivo and in vitro studies have shown that Ang II stimulation induces insulin resistance [ 3536 ].
Interventional studies have documented that angiotensin converting enzyme ACE inhibitors [ 37 ] and angiotensin type 1 receptor blockers [ 38 ] reduce the incidence of T2D in hypertensive patients.
Therefore, the dysregulation of the renin-angiotensin system observed in hypertension is likely to impair insulin signalling and contribute to insulin resistance. Furthermore, it has been reported that an ACE-inhibitor-based long term treatment does not reduce the occurrence of diabetes mellitus in subjects with impaired glucose tolerance [ 39 ].
This observation suggests that the pathophysiological mechanisms underlying the development of insulin resistance in hypertensive patients are partially different from those responsible for impaired insulin sensitivity in diabetics. Ang II acting through angiotensin type 1 AT1 receptor inhibits the actions of insulin via generation of reactive oxygen species ROS by NADPH oxidase [ 40 ].
ROS are important intracellular second messengers. The generation of ROS is implicated in Ang II-induced insulin resistance. At this regard, it has been Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.
The disregulation of neuro-humoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. That in vascular smooth muscle cells VSMC isolated from rat thoracic aorta, Ang II profoundly decreases IRS-1 protein levels via ROS-mediated phosphorylation of IRS-1 on Ser and subsequent proteasome-dependent degradation [ 41 ] Fig.
The key role of ROS in the pathogenesis of Ang II-induced insulin resistance has been also confirmed by in vivo studies. In particular, in rats chronic infusion of Ang II induced hypertension and reduced insulin-evoked glucose uptake during hyperinsulinemic-euglycemic clamp, and increased plasma cholesterylester hydroperoxide levels, indicating an increased oxidative stress.
Treatment with tempol, a superoxide dismutase mimetic, normalized plasma cholesterylester hydroperoxide levels in Ang II-infused rats. In the same setting, tempol normalized insulin resistance in Ang II-infused rats, and enhanced insulin-induced PI3K activation, suggesting that Ang II-induced insulin resistance can be restored by removing the oxidative stress [ 42 ].
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Lancet : — Ohno Y , Suzuki H , Yamakawa H , Nakamura M , Otsuka K , Saruta T Impaired insulin sensitivity in young, lean normotensive offspring of essential hypertensive: possible role of disturbed calcium metabolism. J Hypertens 11 : — Beatty OL , Harper R , Sheridan B , Atkinson AB , Bell PM Insulin resistance in offspring of hypertensive parents. BMJ : 92 — Skarfors ET , Lithell HO , Selinus I Risk factors for the development of hypertension: a year longitudinal study in middle-aged men. J Hypertens 9 : — Lissner L , Bengtsson C , Lapidus L , Kristjansson K , Wedel H Fasting insulin in relation to subsequent blood pressure changes and hypertension in women. Hypertension 20 : — Taittonen L , Uhari M , Nuutinen M , Turtinen J , Pokka T , Akerblom HK Insulin and blood pressure among healthy children. Am J Hypertens 9 : — Raitakari OT , Porkka KVK , Rönnemaa T , Knip M , Uhari M , Akerblom HK , Viikari JSA The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. Diabetologia 38 : — Metabolism 48 : — Meigs JB Invited commentary: insulin resistance syndrome? Syndrome X? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol : — Yeni-Komshian H , Carantoni M , Abbasi F , Reaven GM Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in healthy, nondiabetic volunteers. Diabetes Care 23 : — J Intern Med : — Collins R , Peto R , MacMahon S , Herber P , Fiebach NH , Eberlein KA , Godwin J , Qizilbash N , Taylor JO , Hennekens CH Blood pressure, stroke and coronary heart disease. Short-term reductions in blood pressure: overview of randomized drug trials in their epidemiological context. Reaven GM Relationship between insulin resistance and hypertension. Diabetes Care 14 : 33 — Sheuh WH-H , Jeng C-Y , Shieh S-M , Fuh MM , Shen DD , Chen Y-DI , Reaven GM Insulin resistance and abnormal electrocardiograms in patients with high blood pressure. Jeppesen J , Hein HO , Suadicani P , Gynelberg F High triglycerides and low HDL cholesterol and blood pressure and risk of ischemic heart disease. Hypertension 36 : — Jeppesen J , Hein HO , Suadicani P , Gynterberg F Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Arch Int Med — Reaven GM Treatment of hypertension; focus on prevention of coronary heart disease. J Clin Endocrinol Metab 76 : — Reaven GM Insulin resistance, compensatory hyperinsulinemia, and coronary heart disease: syndrome X. In: Sobell BE, Schneider DJ, eds. Medical management of diabetes and heart disease. New York: Mercel Dekker, Inc. Ross R The pathogenesis of atherosclerosis. Chen N-G , Abbasi F , Lamendola C , McLaughlin T , Cooke JP , Tsao PS , Reaven GM Mononuclear cell adherence to cultured endothelium is enhanced by hypertension and insulin resistance in healthy nondiabetic volunteers. Circulation : — Stuhlinger MC , Abbasi F , Chu JW , Lamendola C , McLaughlin TL , Cooke JP , Reaven GM , Tsao PS Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA : — Vallance P Importance of asymmetrical dimethylarginine in cardiovascular risk. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents The role of insulin resistance and compensatory hyperinsulinemia in the pathogenesis of essential hypertension? Journal Article. Reaven Gerald M. Oxford Academic. PDF Split View Views. Cite Cite Gerald M. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. The role of insulin resistance and compensatory hyperinsulinemia in the pathogenesis of essential hypertension? Figure 1. Open in new tab Download slide. Figure 2. Figure 3. Figure 4. high-density lipoprotein cholesterol;. Serum-insulin in essential hypertension and in peripheral vascular disease. Google Scholar PubMed. OpenURL Placeholder Text. Google Scholar Crossref. Search ADS. Hyperinsulinemia: a link between hypertension, obesity and glucose intolerance. Resistance to insulin-stimulated glucose uptake in patients with hypertension. Insulin resistance, glucose intolerance and hyperinsulinemia in patients with hypertension. Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Hypertension and hyperinsulinemia: a relation in diabetes but not in essential hypertension. An inconsistent relationship between insulin and blood pressure in three Pacific Island populations. Racial differences in the relation between blood pressure and insulin resistance. Insulin resistance, hyperinsulinemia, and blood pressure. Insulinemia and blood pressure: relationships in patients with primary and secondary hypertension, and with or without glucose metabolism impairment. Altered insulin sensitivity, hyperinsulinemia and dyslipidemia in individuals with a hypertensive parent. Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension. Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents. Impaired insulin sensitivity in young, lean normotensive offspring of essential hypertensive: possible role of disturbed calcium metabolism. Risk factors for the development of hypertension: a year longitudinal study in middle-aged men. Fasting insulin in relation to subsequent blood pressure changes and hypertension in women. The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. Hyperinsulinemia in a normal population as a predictor of non-insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: The Barilla factory revisited. Invited commentary: insulin resistance syndrome? Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in healthy, nondiabetic volunteers. Blood pressure, stroke and coronary heart disease. Insulin resistance and abnormal electrocardiograms in patients with high blood pressure. High triglycerides and low HDL cholesterol and blood pressure and risk of ischemic heart disease. Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Google Scholar OpenURL Placeholder Text. Treatment of hypertension; focus on prevention of coronary heart disease. Insulin resistance, compensatory hyperinsulinemia, and coronary heart disease: syndrome X. Mononuclear cell adherence to cultured endothelium is enhanced by hypertension and insulin resistance in healthy nondiabetic volunteers. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. Issue Section:. Download all slides. Views 3, More metrics information. Total Views 3, Email alerts Article activity alert. Advance article alerts. |
| Hypertension and insulin resistance in adipose tissue | There is no reason to suspect that the hyperinsulinemia, glucose intolerance, dyslipidemia, and prothrombotic state associated with the IRS will not contribute to the increased CVD risk in those patients with essential hypertension that are also insulin resistant In addition, changes in endothelial function that might contribute to increased CVD risk also vary as a function of differences in insulin-mediated glucose disposal in patients with essential hypertension. For example, the first step in the process of atherogenesis is the binding of circulating mononuclear cells to the endothelium 34 , and the data in the right panel of Fig. Indeed, it can be seen by comparing the two panels of Fig. Relationship between the SSPG concentration and the adherence of mononuclear cells isolated from the plasma of normal volunteers and patients with essential hypertension to cultured endothelial cells. The SSPG concentration is the average of four measurements of plasma glucose concentration obtained during the last 30 min of a min infusion of somatostatin, glucose, and insulin; the higher the SSPG concentration, the more insulin resistant the individual. Essentially identical findings were observed when the relationship between plasma asymmetric dimethylarginine ADMA concentration and insulin-mediated glucose disposal was evaluated Plasma concentrations of ADMA, an endogenous inhibitor of nitric oxide synthase, have been shown to be predictive of CVD in several clinical syndromes 37 , and Fig. It is apparent that plasma ADMA and SSPG concentrations varied widely in both experimental groups, but it is also obvious that the elevations in plasma ADMA concentrations are associated with higher SSPG concentrations greater degrees of insulin resistance. Thus, plasma ADMA concentrations are increased to a similar degree in insulin-resistant individuals, whether they are normotensive or hypertensive. Relationship between the SSPG concentration and plasma concentration of ADMA concentrations in normotensive and hypertensive individuals. The SSPG concentration is obtained as described in Fig. There is a large body of experimental evidence that insulin resistance and compensatory hyperinsulinemia are increased in prevalence in patients with essential hypertension, and similar changes can be seen in first-degree relatives of patients with essential hypertension. On the other hand, the fact that insulin resistance does not provide a unitarian hypothesis to account for the etiology of essential hypertension should not obscure the large amount of evidence of the importance of insulin resistance, and its metabolic consequences, in both the pathogenesis and clinical course of perhaps as many as half of the patients with essential hypertension. 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Wolpert HA, Steen SN, Istfan NW, Simonson DC. Disparate effects of weight loss on insulin sensitivity and erythrocyte sodium-lithium countertransport activity. Zemel MB, Johnson BA, Ambrozy SA. Insulin-stimulated vascular relaxation. Download references. Cattedra di Medicina Interna, Clinica Medica I, University of Pisa, Pisa, Italy. Salvetti, G. Brogi, V. You can also search for this author in PubMed Google Scholar. Reprints and permissions. Salvetti, A. et al. The Inter-Relationship between Insulin Resistance and Hypertension. Drugs 46 Suppl 2 , — Download citation. Published : 22 October Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Summary Insulin resistance and compensatory hyperinsulinaemia commonly occur in patients with untreated essential hypertension. Access this article Log in via an institution. References Anderson EA, Balon TW, Hoffman RP, Sinkey CA, Mark AL. Hypertension —, a Article PubMed CAS Google Scholar Anderson EA, Gudbjornsdottir S, Elam M, Sellgren J, Mark AL. Abstract Hypertension , b Google Scholar Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Journal of Clinical Investigation —, Article PubMed CAS Google Scholar Andersson O, Sivertsson R, Sannerstedt R, Beckman M, Magnusson M, et al. Body fat and glucose tolerance in early blood pressure elevation: its relation to arteriolar hypertrophy Clinical Science s—s, Google Scholar Baron AD, Brechtel G, Johnson A, Henry D. Hypertension —, Google Scholar Beretta-Piccoli C, Davies DL, Boddy K, Brown JJ, Cumming AMM, et al. Clinical Science —, PubMed CAS Google Scholar Berne C, Fagius J, Niklasson F. Journal of Clinical Investigation —, Article PubMed CAS Google Scholar Bonen A, Tan MH, Watson-Wright WM. 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In the western countries, sedentary life style and hypercaloric food intake are endemic behaviours which play a key role in the development of insulin resistance, mainly through epigenetic modifications. In particular, DNA methylation, histone modifications and noncoding RNA activity miRNA are the principal mechanisms that alter the protein transcription and expression, which, in turn, modify the cellular phenotype. The translocation of GLUT 4 to the cell membrane is the principal step of insulin-induced glucose uptake. Insulin resistance state is characterized by lower expression levels and impaired translocation of GLUT 4. Experimental data indicate that the metilation of DNA, induced by over-nutrition during fetal life, decreases the gene expression of proteins involved in insulin signal transduction, like GLUT 4. The expression of GLUT 4 is also affected by mi RNA. In particular, in myocytes the miRNA b impairs insulin signalling by decreasing insulin-stimulated translocation of GLUT 4. Mitochondrial dysfunction, which also plays a key role in the genesis of insulin resistance, is affected by epigenetic modifications. In particular, methylation of the gene encoding for peroxisome proliferator-activated receptor alpha PPARα has been reported in obese subjects. These data reinforce the hypothesis that epigenetic modifications are at lease partially responsible for the link between behaviour habits and insulin resistance [ 24 ]. In healthy subjects, insulin evokes a net reflex in sympathetic outflow and at the same time it blunts the vasoconstrictive effect resulting from this sympathetic activation. On the contrary, in hypertensive patients insulin evokes a sympathetic activation that is three times greater than in normal subjects, and moreover its vaso-relaxant action is impaired [ 13 ]. This mechanism is involved in dysregulation of peripheral vascular resistance, which contributes to increase BP levels Fig. The key role of insulin resistance in the pathogenesis of hypertension has been further supported by the evidence that in aortic rings of SHR the resistance to the vascular action of insulin is already present at the age of 5 weeks, before the onset of arterial hypertension [ 25 ], suggesting that in SHR vascular resistance to insulin action is specific and not related to the compensatory hyperinsulinemia or hyperglycemia. On the other hand, we have demonstrated, in rats fed for 6 months with hypercaloric diet that the increase of BP and the development of LVH are associated with both hyperinsulinemia or hyperglycemia [ 26 ]. In addition, insulin resistance and the resultant hyperinsulinemia are involved in the development of hypertension-related TOD, through the abnormalities of the counter-regulatory effects of insulin. In particular, impairment of cell membrane ion exchange, enhanced sympathetic nervous and renin-angiotensin systems, suppressed atrial natriuretic peptide activities, sodium retention, and plasma volume expansion contribute to the development of chronic kidney disease, LVH, CA. Regulation of peripheral vascular resistances by insulin and effects of insulin resistance. In physiological conditions, insulin antagonizes green arrows the effects of vasoconstrictor mediators red arrows , contributing to maintain the normal vascular tone. Insulin resistance red arrows , impairs the capability of insulin to counterbalance the action of vasoconstrictor mediators, resulting in the increase of vascular peripheral resistances. TNF-α, tumor necrosis factor-α; IL-6, interleukin Abnormalities of insulin signalling account for insulin resistance. Insulin mediates its action on target organs through phosphorylation of a transmembrane-spanning tyrosine kinase receptor, the insulin receptor IR. The binding of insulin to the α subunit of its receptor activates the tyrosine kinase of the β subunit of the receptor, leading to autophosphorylation, as well as tyrosine phosphorylation of several IR substrates IRS , including IRS-1 and IRS-2 [ 27 ]. These, in turn, interact with phosphatidylinositol 3-kinase PI3K. It is noteworthy that hyperglycaemia, accounts for the development of insulin resistance through the generation of reactive oxygen species ROS , which abrogate insulin-induced tyrosine autophosphorylation of IR [ 29 ]. In particular, phosphorylation of IRS-1 on serine Ser causes dissociation of the p85 subunit of PI3-K, inhibiting further signalling. In addition, phosphorylation of IRS-1 on Ser results in its dissociation from the IR and triggers proteasome-dependent degradation, also impairing insulin signalling. The mechanistic role of abnormalities of IR or IRS-1 signalling in the pathogenesis of insulin resistance and hypertension is supported by several pioneering studies performed in genetically engineered mice. In particular, transgenic mice with targeted disruption of the IRS-1 gene, exhibited higher BP and plasma triglyceride levels compared to wild-type mice. They also showed impairment of endothelium-dependent vascular relaxation [ 33 ]. On the other hand, mice heterozygous for knockout of the IR showed fasting blood glucose, insulin, free fatty acid, and triglyceride levels similar to those of wild-type mice. Interestingly, these mice had increased systolic BP and blunted insulin-stimulated aortic endothelial nitric oxide synthase NOS phosphorylation [ 34 ]. The results of these studies demonstrate that the abnormalities of IR or IRS signalling play a mechanistic role in the development of hypertension, independently form glucose homeostasis and plasma insulin levels, and indicate that insulin resistance by itself is involved the pathogenesis of hypertension. It is noteworthy that IR defects are tissue-specific and depends upon the type of stress; therefore, the insulin resistance phenomenon can be localized in specific tissues and does not necessarily associated with metabolic abnormalities. Several pathophysiological mechanisms contribute to impair insulin signal in hypertension, such as renin angiotensin and sympathetic nervous systems, and oxidative stress. On the other hand, mechanisms playing a protective role against insulin resistance, i. natriuretic peptides are impaired in hypertension. In vivo and in vitro studies have shown that Ang II stimulation induces insulin resistance [ 35 , 36 ]. Interventional studies have documented that angiotensin converting enzyme ACE inhibitors [ 37 ] and angiotensin type 1 receptor blockers [ 38 ] reduce the incidence of T2D in hypertensive patients. Therefore, the dysregulation of the renin-angiotensin system observed in hypertension is likely to impair insulin signalling and contribute to insulin resistance. Furthermore, it has been reported that an ACE-inhibitor-based long term treatment does not reduce the occurrence of diabetes mellitus in subjects with impaired glucose tolerance [ 39 ]. This observation suggests that the pathophysiological mechanisms underlying the development of insulin resistance in hypertensive patients are partially different from those responsible for impaired insulin sensitivity in diabetics. Ang II acting through angiotensin type 1 AT1 receptor inhibits the actions of insulin via generation of reactive oxygen species ROS by NADPH oxidase [ 40 ]. ROS are important intracellular second messengers. The generation of ROS is implicated in Ang II-induced insulin resistance. At this regard, it has been Epidemiological studies have documented a high incidence of diabetes in hypertensive patients. The disregulation of neuro-humoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. That in vascular smooth muscle cells VSMC isolated from rat thoracic aorta, Ang II profoundly decreases IRS-1 protein levels via ROS-mediated phosphorylation of IRS-1 on Ser and subsequent proteasome-dependent degradation [ 41 ] Fig. The key role of ROS in the pathogenesis of Ang II-induced insulin resistance has been also confirmed by in vivo studies. In particular, in rats chronic infusion of Ang II induced hypertension and reduced insulin-evoked glucose uptake during hyperinsulinemic-euglycemic clamp, and increased plasma cholesterylester hydroperoxide levels, indicating an increased oxidative stress. Treatment with tempol, a superoxide dismutase mimetic, normalized plasma cholesterylester hydroperoxide levels in Ang II-infused rats. In the same setting, tempol normalized insulin resistance in Ang II-infused rats, and enhanced insulin-induced PI3K activation, suggesting that Ang II-induced insulin resistance can be restored by removing the oxidative stress [ 42 ]. A further mechanism that account for role of insulin resistance in the aetiology of hypertension is the upregulation of AT1 receptors induced by hyperinsulinemia. This potentiates the detrimental effects of Ang II on cardiovascular CV system. Altogether, these observations provide clear insights of the pathogenic mechanisms of Ang II—induced insulin resistance in the development of hypertension. Molecular mechanisms that account for angiotensin II-induced insulin resistance. The binding of insulin to its own receptor evokes the tyrosine autophosphorylation of the β subunit, which, in turn activates, in sequence, the insulin receptor substrate-1 and phosphatidylinositol 3-kinase green arrows. This cascade, accounts for the biological effects of insulin. Angiotensin II stimulation, through the activation of NADPH oxidase, stimulates the generation of reactive oxygen species, which, in turn promote the threonine phosphorylation of insulin receptor substrate-1 red arrows. This induces the proteasome-dependent degradation of insulin receptor substrate-1, interrupting the insulin signalling cascade. Ser, serine; P, phospho; Tyr, tyrosine; ROS, reactive oxygen species; PI3K, phosphatidylinositol 3-kinase; IRS-1, insulin receptor substrate Dysregulation of sympathetic nervous system is a feature of hypertension [ 44 ]. For instance, adipocytes and cardiac myocytes are both target organs of insulin, and mainly express β3 and β1-ARs, respectively. β-ARs stimulation results in an impairment of insulin signalling and insulin-induced glucose uptake, which profoundly differs between the two cell types regarding the kinetic and molecular mechanisms involved. In particular, β-ARs stimulation in adipocytes impairs insulin signalling within few minutes, whereas, in cardiac myocytes stimulation of β-ARs has a biphasic effect on insulin-stimulated glucose uptake, with an initial additive followed by an inhibitory action. On the contrary, in cardiac myocytes Akt plays a key role in the cross-talk between β1-ARs and IR. Actually, upon the phosphorylation site, Akt can have a favourable or detrimental effect on insulin signalling and insulin-induced glucose uptake. In particular, short-term β-ARs stimulation induces Akt phosphorylation in threonine that results in an increase in glucose uptake, whereas long-term stimulation induces Akt phosphorylation in serine and impairs insulin evoked-glucose uptake and insulin-induced tyrosine autophosporylation of IR [ 46 ]. In addition, it has been demonstrated in cardiac myocytes, that chronic Akt activation is sufficient to impair insulin signal by inducing IRS-1 phosphorylation and proteasome-dependent degradation [ 47 ]. LVH, CA, and renal dysfunction are expression of hypertension-evoked TOD, and are independent risk factors for both fatal and nonfatal cardio- and cerebro-vascular events [ 48 , 49 , 50 , 51 , 52 ]. Several studies have shown that insulin resistance promotes the development of left ventricular hypertrophy, carotid atherosclerosis and chronic kidney disease CKD. Development of LVH is a complex and multifactorial process which involves genetic, hemodynamic and anthropometric components, neuro-hormonal stimulation, growth factors and inflammatory mediators [ 53 , 54 , 55 ]. The hemodynamic and metabolic disorders associated with insulin resistance increase the risk LVH. Insulin and insulin-like growth factor IGF -1 are powerful independent determinants of LV mass and geometry in untreated subjects with essential hypertension and normal glucose tolerance [ 56 ]. The presence of both insulin resistance and hypertension in the same patient results in a mixed pattern of cardiac hypertrophy, caused by an elevation in both cardiac preload and afterload [ 57 ]. Experimental data suggest that insulin might be involved in the pathogenesis of both the concentric and eccentric patterns of LVH. Stimulation of myocardial cell growth and activation of the sympathetic nervous system might preferentially lead to concentric LV hypertrophy through a direct trophic effect and pressure overload, whereas sodium and water retention could lead to eccentric LV hypertrophy through volume overload [ 58 ]. The direct effect of insulin on myocardial cell growth could be mediated, at least in part, by the IGF-1 receptors [ 59 ]. In addition, the myocardium in the insulin-resistant individual shows the presence of mononuclear cell infiltration all along the conduction system making the myocardium in the insulin-resistant hypertensive patient an ideal substrate for cardiac arrhythmia and sudden death. Several epidemiological studies have underlined the role of insulin resistance, hyperinsulinemia in the development of atherosclerosis, and in the pathogenesis of its clinical consequences. Several mechanisms have been proposed as responsible for these phenomena. These include both direct effects on the arterial wall and indirect actions on lipid and glucose metabolism. Considerable evidence exists that demonstrate that endothelium as a physiological target of insulin and, consequently, a potential link between insulin resistance and atherosclerosis. In the endothelium, the stimulation of IRs activates insulin signaling via the PI3-K pathway, leading to NO production. The production of NO by endothelial cells, stimulated by insulin or insulin-like growth factor, leads to a host of anti-inflammatory and antithrombotic effects, which are antiatherogenic. The anti-inflammatory effects of NO include the decreases of expression of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin and reduced secretion of the proinflammatory cytokines monocyte chemoattractant protein—1 and tumor necrosis factor-α TNF-α. Interestingly, the insulin-induced antithrombotic effects depends on gene expression regulation, which decreases the platelet adhesion by increasing prostacyclin production [ 60 ]. Of note, the gene encoding for coagulation factor II thrombin receptor, which is involved in the enhanced risk of coronary artery diseases in patients with hypertension [ 61 ], and it has been recently proposed as a marker of clinical conditions characterized by insulin resistance like metabolic syndromes, obesity, T2D, hepatic steatosis, and atherosclerosis [ 62 ]. Atherosclerotic process is regulated by inflammatory mechanisms [ 63 , 64 , 65 ]. Notably, insulin resistance has been recognized as a chronic, low-level, inflammatory state [ 66 ]. Although several mechanisms may contribute to the pathogenesis of hypertension, the NO system appears to play a major role. NO is an important messenger molecule that plays a critical role in a wide variety of physiological functions, including immune modulation, vascular relaxation, neuronal transmission, and cytotoxicity. Interestingly, the polymorphism of the promoter of the inducible nitric oxide synthase iNOS gene, NOS2A, revealed a positive association with essential hypertension [ 67 ]. This aspect is linked to insulin resistance because insulin stimulation of glucose uptake in skeletal muscle and adipose tissue is a NO-dependent phenomenon. Moreover, iNOS has been shown to be crucial for the development of insulin resistance [ 68 ]. The role that inflammation plays in atherosclerosis is amplified by the renin-angiotensin system via its effects on adhesion molecules, growth factors, and chemoattractant molecules, which modulate the migration of inflammatory cells into the subendothelial space. Clinical and experimental data have increased our knowledge on the effects of the Ang II. In particular, it has been documented that Ang II stimulates the production of ROS through its AT1 receptor [ 69 ], resulting in a proinflammatory modulator. The low grade of inflammation is a common feature of atherosclerosis and insulin resistance. The two major determinants of this state are the pro-inflammatory cytokines, TNF-α and interleukin-6 IL The available experimental data indicate that TNF-α is involved in the pathophysiology of hypertension. In particular, in vitro, TNF-α stimulates the production of endothelin-1 and angiotensinogen. Moreover, in SHR, TNF-α synthesis and secretion and fat angiotensinogen mRNA are increased in response to lipopolysaccharide LPS stimulation in comparison with non-hypertensive control rats [ 70 ]. At molecular level, TNF-α blocks the action of insulin in cultured cells [ 71 ], though the serine phosphorylation of IRS-1, decreasing the tyrosine kinase activity of the insulin receptor [ 72 ]. The key role of TNF-α in the pathogenesis of hypertension has been also documented in humans. In particular, the TNF-α gene locus seems to be involved in insulin resistance-associated hypertension [ 73 ]. A positive correlation has been found between serum TNF-α concentration and both SBP and insulin resistance [ 74 ]. Up-regulation of TNF-α secretion has also been observed in peripheral blood monocytes from hypertensive patients [ 75 ]. TNF-α also determines endothelial dysfunction linked to insulin resistance [ 76 ]. In contrast, treatment of T2D or obese human subjects with an antibody specific for TNF had no effect on insulin sensitivity [ 78 ]. IL-6 is a multifunctional cytokine produced by many different cell types, including immune cells, endothelial cells, fibroblasts, myocytes, and adipose tissue, which mediates inflammatory as well as stress-induced responses. It has been documented that BP was a significant and independent predictor of circulating IL-6 concentrations in women but not in men [ 79 ]. A polymorphism in the promoter of the IL-6 gene has also shown divergent associations with BP [ 80 ]. IL-6 stimulates the central nervous system and the sympathetic nervous system, which may result in hypertension [ 81 ]. However, other mechanisms cannot be excluded. IL-6 might increase in parallel to the modification of the redox state of the vascular wall in chronic hypertension, as occurs in some animal models of hypertension [ 82 ]. IL-6 is a well-characterized acute inducer of fibrinogen, which is a determinant of blood viscosity. Finally, IL-6 might increase BP enhancing the expression of angiotensinogen, leading to higher concentration of Ang II. Interestingly, leptin, a cytokine-like molecule increasingly recognized to regulate several inflammatory pathways acting on a receptor of the IL-6 family seems also to be associated with hypertension. The leptin signal, via central leptin receptors, is believed to interact with the central sympathetic nervous system [ 83 ]. Infusion of leptin leads to increases in BP [ 84 ]. Transgenic mice overexpressing leptin had elevated BP, which is normalized by adrenergic and ganglionic blockade [ 85 ]. Hypertension is believed to contribute to CKD by increasing glomerular capillary pressure, proteinuria, endothelial dysfunction, and sclerosis, leading to nephron damage [ 86 ]. Insulin resistance is associated with activation of both renin-angiotensin system and sympathetic nervous system activities, contributing to increased renal sodium reabsorption, associated fluid retention and hypertension [ 87 ]. Moreover, this state is accompanied by the increased endothelial cells proliferation and intrarenal lipid and hyaluronate deposition in the matrix and inner medulla [ 88 ]. These depositions increase intrarenal pressure and volume in the tightly encapsulated kidney, leading to parenchymal prolapse and urine outflow obstruction, which result in slow tubular flow and subsequently increased sodium reabsorption, especially in the loop of Henle. These functional and structural changes provoke compensatory lowered renal vascular resistance, elevated kidney plasma flow, glomerular hyperfiltration, and stimulation of renin angiotensin system, despite volume expansion. In addition, these changes in combination with the raise in BP levels associated with the insulin-resistant state increase the tubular reabsorption and maintain sodium balance. The persistence of these compensatory responses, increasing glomerular wall stress, precipitate gradual nephron loss, glomerulosclerosis and eventually end-stage renal disease. Glomerulosclerosis in the insulin-resistant kidney is peculiar and characterized by lower rate of nephrotic syndrome, fewer lesions of segmental sclerosis and a greater glomerular size compared with the idiopathic variety. In summary, persistence of insulin resistance and suboptimal control of associated hemodynamic and metabolic abnormalities cause renal injury with functional as well as structural nephron loss contributing to elevated BP, which in turn leads to further renal injury, thereby setting off a vicious circle of events leading to further elevated BP and renal injury. Microalbuminuria is now established as a modifiable predictor of CV morbidity and mortality [ 52 , 89 ] and is considered a manifestation hypertension-induced TOD. Despite its strong association with CV risk, the exact pathogenic mechanisms that link microalbuminuria to CV diseases remains unknown. Evidence has been garnered that microalbuminuria is a marker of generalized endothelial dysfunction and consequently a risk factor for CV diseases. In particular, this abnormality has been characterized by the presence of transmembrane leakiness [ 90 ]. In addition, microalbuminuria has also been associated with alterations in hemodynamic and vascular responses. In general, microalbuminuria can be considered as an early marker of generalized hypertension-evoked TOD Fig. Relationship between microalbuminuria and insulin resistance in the continuum of cardiovascular disease. Microalbuminuria, is clinical marker of activation of the insulin resistance-dependent pathogenic mechanisms involved in the genesis and progression of hypertension and hypertension-induced target organ damage. Epidemiological data show that hypertension is a risk factor for the development of T2D. The combination of hypertension and T2D increases CV risk and requires a strict control of both BP and glycaemia [ 91 ]. Insulin resistanceis involved in the pathogenesis and progression of hypertension as well as T2D. The low-grade of inflammation induced by insulin resistance is the principal mechanism that accounts for development of endothelial dysfunction, hypertension-induced TOD, and metabolic abnormalities [ 92 ] Fig. Altogether these data encourage the adoption of a holistic strategy to prevent the development of insulin resistance. In particular, it is well known that hypocaloric diet, and regular exercise training improve insulin sensitivity [ 93 ]. Both are recommended for primary and secondary CV prevention. It is noteworthy that consistent body of evidence supports the notion that exercise training is able to modify the epigenetics changes that are involved in the development of insulin resistance [ 24 ]. Insulin resistance is a time-dependent organ and tissue specific phenomenon. Insulin resistance contributes to the dysregulation of peripheral vascular resistance, resulting in an increase of blood pressure. In arterial hypertension, insulin resistance participates to the development of target organ damage. The persistence of insulin resistance induces the metabolic abnormalities that account for development of type 2 diabetes. The increased caloric intake and the sedentary habit are the principal environmental factors that account for the development and progression of insulin resistance. The dysregulation of renin-angiotensin system plays a pivotal role in the development of insulin resistance; thus, the prevention of incident T2D in patients with hypertension requires the inhibition of RAS with AT1 antagonist or ACE inhibitors [ 94 ]. Finally, in the last decades the beneficial effects on the CV system of different classes of glucose-lowering agents have been reported. In particular, Glucagon-like peptide-1 receptor agonists GLP-1RAs stimulate insulin release and supress glucagon synthesis. There is growing body of evidence that the GLP-1RAs improve CV outcomes in type 2 diabetes. In fact, they are recommended as first- and second-choice agents in diabetic patients at high CV risk or with overt atherosclerosis, independently from achievement of glycemic control [ 95 , 96 ]. In conclusion, the prevention of the insulin resistance-induced continuum of CV disease requires an integrated approach which involves non pharmacologic and pharmacologic therapies. 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| Insulin resistance/compensatory hyperinsulinemia and CVD | Also, the prevalence of muscle type 2b fibres fast twitch fibres may contribute to the development of insulin resistance. The common pathogenetic mechanism for both insulin resistance and hypertension could be activation of the sympathetic nervous system. This results in vasoconstriction, and may contribute to the genesis of vascular structural changes and increase the number of fast twitch fibres. Abstract Insulin resistance and compensatory hyperinsulinaemia commonly occur in patients with untreated essential hypertension. Publication types Review. Kramer CK, von Mühlen D, Barrett-Connor E. Mid-life blood pressure levels and the 8-year incidence of type 2 diabetes mellitus: the Rancho Bernardo study. J Hum Hypertens. Stahl CH, Novak M, Lappas G, Wilhelmsen L, Björck L, Hansson P-O, Rosengren A. High-normal blood pressure and long-term risk of type 2 diabetes: year prospective population based cohort study of men. 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Open access funding provided by Università degli Studi di Napoli Federico II within the CRUI-CARE Agreement. Giuseppe Di Gioia received a grant from the Cardiopath PhD program. CM and CM had the idea for this article, RI, MAL, and GDG, performed the literature search, CM and CM drafted, and EB critically revised the work. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Mancusi, C. et al. Insulin Resistance the Hinge Between Hypertension and Type 2 Diabetes. High Blood Press Cardiovasc Prev 27 , — Download citation. Received : 25 July Accepted : 05 September Published : 22 September Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Download PDF. Abstract Epidemiological studies have documented a high incidence of diabetes in hypertensive patients. Management of hyperglycaemia in type 2 diabetes, A consensus report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD Article 24 September Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus Article 10 March Metformin: clinical use in type 2 diabetes Article 02 August Use our pre-submission checklist Avoid common mistakes on your manuscript. Full size image. References Conen D, Ridker PM, Mora S, Buring JE, Glynn RJ. PubMed Google Scholar Meisinger C, Döring A, Heier M. 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| Background | Insuli Supercharge your metabolism Clinical Investigation —, Article Google Scholar Pressude Legge V, Prwssure L, Energy recovery systems AR, Ciccarone A, Lenzi M, et al. Effects resietance Supercharge your metabolism peroxisomal proliferator-activated receptor-γ agonist pioglitazone on renal and hormonal responses to salt in healthy men. Meigs JB Invited commentary: insulin resistance syndrome? Informed consent was obtained from all subjects. Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A, Tsuneyama K, et al. Zinn, A. Klein J, Fasshauer M, Ito M, Lowell BB, Benito M, Kahn CR. |
| Frontiers | Salt-Sensitivity of Blood Pressure and Insulin Resistance | Xnd ancestors were caloric restriction and lifespan faced prsesure survival resixtance, including famine, infection, Supercharge your metabolism bloo physical stress. In Insulin resistance and high blood pressure second study 31the participants an in the Copenhagen Male Study were divided into three groups on the basis of their fasting plasma TG and HDL-C concentrations. Prehypertension was defined as SBP values of — mmHg or DBP values of 80—89 mmHg on the second visit, in individuals without antihypertensive medication use. Hypertension, angiotensin ii, and oxidative stress. Baron AD, Brechtel G, Johnson A, Henry D. γδ T cells mediate angiotensin II-induced hypertension and vascular injury. |
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