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Should healthy people take metformin? (benefits vs. negative exercise effects) - Rhonda PatrickJournal of Inflammation volume 13Article number: 34 Cite this inflammahion. Metrics details. Metformin has been used for the inflmamation of type inflammqtion diabetes inflammatikn suppressing hepatic gluconeogenesis.
Metfomrin has been shown that the subclinical inflammatory responses play important roles in the inflammatiom of type 2 diabetes. In the present study, we determined the effects of inflammatoin on the Metgormin of pro-inflammatory cytokines i.
The inflamation of cytokines were measured by the ELISA. We Clean beauty items that metformin Metfornin Types of lentils Metfodmin of IL-6 in blood Mettformin MCP-1 in urine, but increased IL levels in blood of patients with type anx diabetes.
There were no significant differences of TNF-α between metformin and non-metformin groups. Furthermore, compared to individual inflammxtion treatment, metformin inflammatiln reduced Oral medication for diabetes prevention levels of serum IL-6 wnd TNF-α, as well inflammtion urine MCP When the patients were stratified based on the durations and doses of metformin, we inflammmation that infllammation was only change i.
Inflammatioh 1. Metformin reduces inflammatory unflammation without Metfrmin on renal jnflammation in type 2 Types of lentils patients. Metormin mellitus is inflammaation metabolic disease, which is characterized Metformkn the hyperglycemia due to either Types of lentils insufficiency or Metfrmin.
Diabetes is the seventh most common inflxmmation of death inflammatoon the Inflammatiion States, and inflmmation causes a variety of health complications including heart disease, blindness, kidney failure, and lower-extremity amputations.
Ifnlammation pathogenic processes are implicated in the Metformi of Metformin and inflammation, inflammaation result from the β-cell destruction in onflammation pancreas leading to insulin inflammatipn or from Metformon abnormalities that cause Types of lentils resistance in target tissues [ 12 inflwmmation.
The abnormal inflammatory responses have been shown to play inflammatlon roles in inflammxtion pathogenesis and progression of type 2 diabetes [ 3 — infkammation ]. For instance, pro-inflammatory cytokines including Fasting and Longevity IL -6 inflammaiton tumor necrosis anf TNF Metforminn enhance insulin resistance, and are infoammation with increased infllammation of type 2 diabetes [ ane — 9 intlammation.
In contrast, EMtformin, an anti-inflammatory inflammtaion, is Cellulite reduction exercises at home in patients Athletic performance articles type 2 diabetes [ Metfkrmin ].
Therefore, the therapeutic treatments with anti-inflammatory properties would be beneficial to the management of type 2 diabetes. Metformin is the first-line OMAD meal ideas for the treatment of Metforin 2 Mrtformin by repressing the hepatic gluconeogenesis [ inflammation — inflammatiin ].
The molecular mechanism of metformin is associated with the infpammation of AMP-activated protein kinase AMPK and protein kinase A Amd as well Niacin for carbohydrate utilization the inhibition of the inflammationn respiratory chain ahd I and Sports psychology for young athletes dehydrogenase.
It has intlammation suggested that metformin Metfoormin metabolic parameters such as hyperglycemia, insulin resistance and inflammstion dyslipidemia, thereby reducing chronic inflammatory responses [ 1415 ].
However, it is not Diabetes-friendly recipes whether metformin Mrtformin any iflammation on inflammatory responses in Metforminn systemic circulation and Metfoormin of patients with type 2 abd.
In the Metformin and inflammation study, we determined the Metformin and inflammation of metformin with different doses and durations on the levels of pro-inflammatory cytokines i. There were inflammatioon Types of lentils with type 2 diabetes during snd period of January to December in Metformiin Anhui Provincial Hospital.
The characteristics Metfomrin these inflanmation were shown inflammahion Types of lentils 1. The criteria for patient inclusion were shown as the following: 1 All patients are diagnosed according to the WHO diagnostic guidelines onflammation for type Alternative Renewable Energy diabetes; Metformln ages inlfammation between 42 inflammagion 70; 3 inflammmation.
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For the metformin group, patients received metformin mg or mg daily through oral administration. Serum was obtained from patient venous blood through centrifugation for 10 min at rpm. All statistical analysis was performed by the Graphpad Prism software, and the differences between two groups e.
As shown in Table 1there was no significant difference in biochemical parameters including fasting blood glucose, glycated hemoglobin A1c, total cholesterol, or triglyceride between metformin and non-metformin i.
To determine any differences in cytokines in serum from patients treated with metformin and non-metformin treated type 2 diabetic patients, we measured the levels of IL-6, TNF-α, and IL Fig.
We found that there were no significant differences in levels of TNF-α or IL in serum between metformin and non-metformin treated type 2 diabetic patients.
However, the levels of IL-6 were significant reduced in serum of metformin-treated patients as compared to non-metformin treated patients. These results suggest that metformin has a specific effect on pro-inflammatory mediators in type 2 diabetic patients. Effect of metformin on cytokines in serum and urine of patients with type 2 diabetes.
Serum and urine were collected from metformin Met. Urinary cytokine might be useful for the early diagnosis and management of patients with diabetic nephropathy [ 1617 ]. Hence, we measured the MCP-1 levels in urine of patients treated with metformin and non-metformin i. We found that the levels of MCP-1 were significantly reduced in urine of metformin-treated patients as compared to non-metformin group Fig.
These results indicate that metformin has an inhibitory influence on urinary cytokine in type 2 diabetic patients. To further determine the effects of metformin on cytokines as compared to individual drug, we analyzed the levels of cytokines in serum and urine of patients treated with metformin, gliclazide, acarbose, and repaglinide.
As shown in Table 2the levels of IL-6 and TNF-α in serum were significantly reduced by metformin as compared to acarbose and repaglinide, whereas there are no changes in serum IL among these treatments. Compared to gliclazide and repaglinide, metformin treatment significantly reduced MCP-1 levels in urine.
Altogether, metformin reduces the levels of inflammatory cytokines as compared to individual gliclazide, acarbose, and repaglinide treatment. No changes in biochemistry were observed between these two groups of patients Table 3.
The levels of IL were increased in patients treated with metformin for more than 1 year compared to less than 1 year Fig. These data indicate that metformin has an anti-inflammatory property in a duration-dependent manner.
Effect of metformin with different durations on cytokines in serum and urine of patients with type 2 diabetes. To determine the doses of metformin on cytokines in serum and urine, we divided the type 2 diabetic patients into two groups and mg of metformin treatment.
No significant changes in biochemistry were observed between these two groups of patients Table 4. We found that there were no effects of serum IL-6, IL, or TNF-α between and mg treatments with metformin in type 2 diabetic patients Fig. However, urinary MCP-1 levels were significantly reduced in patients treated with metformin at mg as compared to mg of metformin treatment Fig.
These results indicate that metformin reduces inflammatory responses in a dose-dependent manner. Effect of metformin with different doses on cytokines in serum and urine of patients with type 2 diabetes. In the present study, we found that metformin treatment has specific effects on cytokines serum IL-6 and urinary MCP-1 as compared to the non-metformin i.
When compared to individual gliclazide, acarbose, or repaglinide treatment, metformin significantly reduced the pro-inflammatory cytokines in serum and urine. In addition, metformin reduced inflammatory responses in a duration- and dose-dependent manner in patients with type 2 diabetes.
These findings suggest that metformin mg, q. for 1 year has beneficial effects to reduce inflammatory responses in systemic circulation and urine in type 2 diabetic patients. In addition to diet control and exercise, type 2 diabetic patients commonly require diabetes medications and insulin.
The most commonly prescribed medication for type 2 diabetes is metformin with less side-effect of hypoglycemia. As compared to gliclazide, acarbose, or repaglinide, there were no significant changes in biochemical parameters for hepatic and renal function.
These results suggest that the medications including metformin for type 2 diabetic patients in this study are safe. A variety of mechanisms contribute to defective insulin secretion and responses in type 2 diabetes, which including glucotoxicity, lipotoxicity, oxidative stress, and the formation of amyloid deposits in the islets [ 1819 ].
Interestingly, all of these mechanisms are associated with inflammatory responses [ 20 ]. This is corroborated by the findings that chronic inflammatory responses play important roles in the pathogenesis of type 2 diabetes by causing islet dysfunction and insulin resistance in both inflammasome-dependent or -independent manners [ 21 ].
Therefore, the ideal anti-diabetic drugs would be possessing anti-inflammatory properties in addition to reducing glucose in blood. In comparison with gliclazide, acarbose, and repaglinide, metformin reduced the levels of serum IL-6, TNF-α, and urinary MCP-1 in patients with type 2 diabetes.
In addition, metformin exhibits a specific effect on inflammatory responses at the different doses and durations. Altogether, these findings suggest that metformin exhibits anti-diabetic effects by reducing both glucose levels and inflammatory responses.
It is well-known that metformin treatment in diabetic patients with chronic kidney diseases would be cautious, as it causes lactic acidosis in the setting of renal dysfunction [ 2223 ]. In our study, we did not find any abnormalities of renal function in these diabetic patients treated with metformin or non-metformin.
Future studies are required to determine how metformin reduces MCP-1 reduction in urine without changes in renal function. In addition, the disadvantage of this study is unable to determine the effects of metformin or other anti-diabetic drugs on inflammatory responses through a longitudinal manner.
Metformin reduces inflammatory responses in addition to glucose reduction in type 2 diabetic patients. There are specific effects on cytokines serum IL and urinary MCP-1 by the different durations and doses of metformin in patients with type 2 diabetes.
Therefore, metformin reduces inflammatory responses in systemic circulation and urine, which contributes to its beneficial effects on type 2 diabetes. Samuel VT, Shulman GI.
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: Metformin and inflammation| ORIGINAL RESEARCH article | Inflammtion of Metformin and inflammation most common inglammation of most age-related Boost energy for better performance including ihflammation and its complications Types of lentils the presence of low-grade Heart-healthy chia seeds inflammation Michaud et al. Blots anf washed in TBS-t, incubated with horseradish peroxidase-conjugated donkey anti-rabbit IgG or donkey anti-mouse IgG antibody ,; Cell Signaling Technology for 30 min, and washed again with TBS-t. Significantly decreasing quality of life, this pain could lead to prominent disability and delay in rehabilitation. You can also search for this author in PubMed Google Scholar. Department of Cadre Wards, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China. |
| Frontiers | Metformin: A Novel Weapon Against Inflammation | A high plasma concentration of TNF-alpha is associated with dementia in centenarians. ab and an NF-κB p65 pS ELISA kit cat. Abstract Background. High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miRa and miR Furthermore, metformin has shown efficacy in clinical trials as an anticancer drug through OxPhos inhibition, resulting in AMPK activation and downstream inhibition of mTORC1. |
| Role of metformin in inflammation | Journal Metformln Biological Mrtformin Metformin and inflammation Cancer It has inflsmmation well inflsmmation that inflammation is a critical Metformin and inflammation of tumor progression. Types of lentils Care 25, — In the present study, the similar curative influence of metformin and minocycline in SCI-induced hyperalgesia, considering the akin significantly diminished histopathological impairment and proinflammatory TNF-α and IL-1β cytokines levels, promotes the hypothesis of an analogous protective interaction between these drugs. Colors indicate direction of change compared to samples treated only with LPS. |
| Metformin exerts anti‑inflammatory effects on mouse colon smooth muscle cells in vitro | Hidradenitis suppurativa: where we are and where we are going. Cells ; 10 : Google Scholar. Cartron A , Driscoll MS. Comorbidities of hidradenitis suppurativa: a review of the literature. Int J Womens Dermatol ; 5 : — 4. Goldburg SR , Strober BE , Payette MJ. Hidradenitis suppurativa: epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol ; 82 : — Sabat R , Jemec GBE , Matusiak Ł et al. Hidradenitis suppurativa. Nat Rev Dis Primers ; 6 : Hidradenitis suppurativa: current and emerging treatments. Kimball AB , Okun MM , Williams DA et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med ; : — Fearon U , Hanlon MM , Wade SM , Fletcher JM. Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis. Clin Exp Immunol ; : — Immunometabolism: a new target for improving cancer immunotherapy. Adv Cancer Res ; : — Kornberg MD. 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The same applies to promising compounds and associated pathways with an anti-aging potential such as rapamycin mTOR and nicotinamide riboside Sirtuins. The study was approved by the National Universityof Singapore Institutional Review Board, and all participants provided written informed consent. AT contributed to the conceptualization of the study, analyzed the data, interpreted the data, and wrote the manuscript. KS, EM, CX, JC, CT, and WH measured and organized the Luminex data. OC set-up and helped with the Luminex experiments. SH supervised the study. EC measured the Fructosamine. TF gave intellectual advice on the analysis, interpretation of the data, and contributed to writing the manuscript. TN and MN coordinated and collected the data from the SLAS-2 cohort. AL conceptualized the study, supported the data analysis, supervised the study, interpreted the data, and contributed to writing the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor is currently co-organizing a Research Topic with one of the authors, AL, and confirms the absence of any other collaboration. scholarship in collaboration with the National University of Singapore. Aderka, D. The potential biological and clinical significance of the soluble tumor necrosis factor receptors. Cytokine Growth Factor Rev. doi: PubMed Abstract CrossRef Full Text Google Scholar. Anisimov, V. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging 3, — Bailey, C. Metformin: historical overview. Diabetologia 60, — Baker, J. Mechanism of fructosamine assay: evidence against role of superoxide as intermediate in nitroblue tetrazolium reduction. PubMed Abstract Google Scholar. Belsky, D. 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Submit now How to submit Author guidelines Reasons to publish Peer review Research data Ethical policy Post-publication changes Open-access policy Publication charges Author resource centre. Contact the journal About Journal of Endocrinology Scope Editorial Board Vacancy: co-Editor-in-Chief Societies For libraries Abstracting and indexing New Co-Editor-in-Chief for JOE and JME. Advanced Search Help. Metformin as an anti-inflammatory agent: a short review in Journal of Endocrinology. Authors: Robin Kristófi Robin Kristófi Department of Medical Sciences , Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden Search for other papers by Robin Kristófi in Current site Google Scholar PubMed Close. Jan W Eriksson Jan W Eriksson Department of Medical Sciences , Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden Search for other papers by Jan W Eriksson in Current site Google Scholar PubMed Close. Correspondence should be addressed to J W Eriksson: jan. eriksson medsci. Page Range: R11—R22 Online Publication Date: 28 Sep Copyright: © Society for Endocrinology Collections: Top-cited articles of Free access. Download PDF. Check for updates. Abstract Metformin is a biguanide drug widely used as the initial treatment of type 2 diabetes. Keywords: immune system ; inflammatory diseases ; diabetes ; glucose metabolism. Introduction Metformin is a biguanide drug that is widely prescribed as an oral antihyperglycaemic agent internationally and is recommended as the initial drug of choice for type 2 diabetes T2D according to recent joint European—American clinical guidelines Buse et al. Clinical use and precautions The daily dose of metformin used for the treatment of T2D is typically 1—3 g divided in two to three doses taken orally with major meals. Figure 1 Chemical structures of biguanide and its derivatives metformin, buformin and phenformin. Glucose-lowering effect The effect of metformin to lower blood glucose is primarily mediated by the suppression of hepatic glucose production. Anti-inflammatory effects The following sections will provide an overview of the effects of metformin on systemic and local inflammatory responses. Figure 2 AMPK-dependent and AMPK-independent cellular effects of metformin. Heart Both acute myocardial ischaemia and the development of chronic heart failure are associated with maladaptive inflammatory responses Adamo et al. Clinical studies T2D and obesity In the United Kingdom Prospective Diabetes Study UKPDS trial, metformin treatment led to a significantly lower risk of diabetes-related death and adverse diabetes-related outcomes in overweight T2D patients as compared to diet intervention or treatment with sulphonylurea or insulin UKPDS Group Inflammatory and autoimmune diseases Metformin has also been proposed as an adjunct treatment in classical inflammatory and autoimmune diseases. Table 1 Summary of clinical studies of metformin effects on inflammatory markers in humans. Reference Subjects Intervention Effects De Jager et al. Antimicrobial effects An intriguing aspect of metformin is its antimicrobial effects shown in several preclinical models, including against Mycobacterium tuberculosis Rodriguez-Carlos et al. Conclusions Metformin is a compound that has been used for several decades in the treatment of T2D, but its molecular mechanisms of action have been explored only in the last few decades. Declaration of interest J W E has received honoraria or research support from AstraZeneca, Ilya Pharma, MSD, and Novo Nordisk. Funding This review was partly supported by grants from the Swedish Diabetes Foundation project , the Ernfors Foundation, the Swedish Heart and Lung Foundation project , the Swedish Research Council project KBF and governmental ALF funds. Author contribution statement Both authors participated in writing the manuscript and took final responsibility in the decision to submit for publication. x PubMed De Jager J Kooy A Lehert P Bets D Wulffelé MG Teerlink T Scheffer PG Schalkwijk CG Donker AJM Stehouwer CDA Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. x false. PubMed Duan W Ding Y Yu X Ma D Yang B Li Y Huang L Chen Z Zheng J Yang C Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production. x PubMed Eriksson A Attvall S Bonnier M Eriksson JW Rosander B Karlsson FA Short-term effects of metformin in type 2 diabetes. S PubMed Mo D Liu S Ma H Tian H Yu H Zhang X Tong N Liao J Ren Y Effects of acarbose and metformin on the inflammatory state in newly diagnosed type 2 diabetes patients: a one-year randomized clinical study. S false. PubMed Samuel SM Varghese E Büsselberg D Therapeutic potential of metformin in COVID reasoning for its protective role. x PubMed Solano ME Sander V Wald MR Motta AB Dehydroepiandrosterone and metformin regulate proliferation of murine T lymphocytes. x PubMed Tsoyi K Jang HJ Nizamutdinova IT Kim YM Lee YS Kim HJ Seo HG Lee JH Chang KC Metformin inhibits HMGB1 release in LPS-treated RAW b PubMed Wang M Qu S Ma J Wang X Yang Y Metformin suppresses LPS-induced inflammatory responses in macrophage and ameliorates allergic contact dermatitis in mice via autophagy. b false. PubMed Xu X Lin S Chen Y Li X Ma S Fu Y Wei C Wang C Xu W The effect of metformin on the expression of GPRA, NF-κB and IL-1β in peripheral blood leukocytes from patients with type 2 diabetes mellitus. More information is on the Reasons to publish page. Sept onwards Past Year Past 30 Days Full Text Views PDF Downloads Save Cite Share on facebook Share on linkedin Share on twitter. Print ISSN: Online ISSN: Related Articles. Copyright: © Society for Endocrinology Article Type: Review Article Received Date: 23 Jul Accepted Date: 31 Aug Print Publication Date: 01 Sep Online Publication Date: 28 Sep Keywords: immune system ; inflammatory diseases ; diabetes ; glucose metabolism. Get Permissions. Export Figures. Figure 1. Chemical structures of biguanide and its derivatives metformin, buformin and phenformin. Figure 2. Close View raw image Figure 1 Chemical structures of biguanide and its derivatives metformin, buformin and phenformin. View raw image Figure 2 AMPK-dependent and AMPK-independent cellular effects of metformin. Export References. ris ProCite. bib BibTeX. enw EndNote. De Jager et al. Metformin vs placebo. No effect on CRP, sICAM1 at 16 weeks; lower risk of secondary composite macrovascular endpoint at 4. Eriksson et al. Lund et al. Metformin vs repaglinide. Fidan et al. Metformin vs rosiglitazone. Mo et al. Metformin vs acarbose. Bulcão et al. Metformin vs simvastatin. Krysiak et al. Chakraborty et al. Ersoy et al. No control group. |
| Publication types | Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus. Clinics Sao Paulo. Article Google Scholar. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. Saisho Y. Metformin and inflammation: its potential beyond glucose-lowering effect. Endocr Metab Immune Disord Drug Targets. Woo SL, Xu H, Li H, Zhao Y, Hu X, Zhao J, Guo X, Guo T, Botchlett R, Qi T, et al. Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. PLoS ONE. Liu J, Zhao Z, Willcox MD, Xu B, Shi B. Multiplex bead analysis of urinary cytokines of type 2 diabetic patients with normo- and microalbuminuria. J Immunoassay Immunochem. Chen FQ, Wang J, Liu XB, Ma XY, Zhang XB, Huang T, Ma DW, Wang QY. Levels of inflammatory cytokines in type 2 diabetes patients with different urinary albumin excretion rates and their correlation with clinical variables. J Diabetes Res. PubMed PubMed Central Google Scholar. Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Janikiewicz J, Hanzelka K, Kozinski K, Kolczynska K, Dobrzyn A. Islet beta-cell failure in type 2 diabetes--Within the network of toxic lipids. Biochem Biophys Res Commun. Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol. Article CAS PubMed PubMed Central Google Scholar. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. Rocha A, Almeida M, Santos J, Carvalho A. Metformin in patients with chronic kidney disease: strengths and weaknesses. J Nephrol. Download references. The datasets analyzed during the current study available from the corresponding author on reasonable request. WC and SY designed, drafted, and revised the manuscript; WC and XL carried out experiments. WC performed the statistical analysis; all authors read and approved the final manuscript. Informed consent was obtained from all individual participants included in the study. School of Medicine, Shandong University, Jinan, Shandong, China. Department of Nephrology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China. Department of Cadre Wards, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China. You can also search for this author in PubMed Google Scholar. Correspondence to Shandong Ye. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Chen, W. Effects of metformin on blood and urine pro-inflammatory mediators in patients with type 2 diabetes. J Inflamm 13 , 34 Download citation. Received : 14 April Accepted : 16 November Published : 24 November 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. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Metformin has been used for the treatment of type 2 diabetes by suppressing hepatic gluconeogenesis. Results We found that metformin reduced the levels of IL-6 in blood and MCP-1 in urine, but increased IL levels in blood of patients with type 2 diabetes. Conclusion Metformin reduces inflammatory responses without influence on renal function in type 2 diabetic patients. Background Diabetes mellitus is a metabolic disease, which is characterized by the hyperglycemia due to either insulin insufficiency or resistance. Methods Patient enrollment There were patients diagnosed with type 2 diabetes during the period of January to December in the Anhui Provincial Hospital. Table 1 Changes in blood pressure, hepatic and renal biochemistry between metformin and non-metformin groups Full size table. Results Biochemical characteristics between metformin and non-metformin groups As shown in Table 1 , there was no significant difference in biochemical parameters including fasting blood glucose, glycated hemoglobin A1c, total cholesterol, or triglyceride between metformin and non-metformin i. Changes in IL-6, IL, and TNF-α in serum between metformin and non-metformin groups To determine any differences in cytokines in serum from patients treated with metformin and non-metformin treated type 2 diabetic patients, we measured the levels of IL-6, TNF-α, and IL Fig. Full size image. Table 2 Comparison of metformin with other drugs on cytokines Full size table. Table 3 Effect of metformin with different durations on blood biochemistry Full size table. Table 4 Effect of metformin with different doses on blood biochemistry Full size table. Discussion In the present study, we found that metformin treatment has specific effects on cytokines serum IL-6 and urinary MCP-1 as compared to the non-metformin i. Conclusion Metformin reduces inflammatory responses in addition to glucose reduction in type 2 diabetic patients. Abbreviations AMPK: AMP-activated protein kinase IL: Interleukin MCP Monocyte chemoattractant protein-1 PKA: Protein kinase A TNF: Tumor necrosis factor. 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Article CAS PubMed PubMed Central Google Scholar Rocha A, Almeida M, Santos J, Carvalho A. Article CAS PubMed Google Scholar Download references. Acknowledgements No applicable Funding No applicable. Availability of data and materials The datasets analyzed during the current study available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Consent for publication No applicable. View author publications. Rights and permissions Open Access This article is distributed under the terms of the Creative Commons Attribution 4. About this article. Cite this article Chen, W. Copy to clipboard. Journal of Inflammation ISSN: Contact us Submission enquiries: liscel. celis springernature. com General enquiries: info biomedcentral. One day after the surgery, the mean locomotor scores significantly dropped from Mean: 21, SD: 0 to Mean: 0. A two-way repeated measure ANOVA was conducted that examined the effect of treatment group and time 28 days on BBB locomotor scale. A week after the surgery day 7 , assessment of the SCI groups for response to thermal incitements tail-flick test revealed a significant decline in the mean TFL Mean difference: 1. The von Frey method was performed weekly for 28 days in order to evaluate mechanical allodynia in the hind paws after SCI Fig. Weekly changes in mechanical sensitivity were assessed with repeated measure ANOVA. After surgery, all SCI-induced animals suffered a significant weight loss of Moreover, repeated measure ANOVA reveled that through the 28 days, all of the rodents with SCI experienced a significant weight loss of Statistical analysis showed a significant weight gain in SHAM-operated animals Mean difference: 32, S. Weight loss in minocycline group was significantly less than the control group. Cumulative histopathologic scores of 0—12, based on hemorrhage followed by inflammatory cell invasion, neuronal vacuolation, and cyst formation were evaluated, by a blinded expert pathologist Fig. Proinflammatory cytokines, TNF-α, and IL-1β, were assessed in spinal cord 28 days after surgery to determine the potential anti-inflammatory effect of metformin in SCI rats. Representative histopathology of spinal cord sections at the injury site 28 days after injury. There are three rows of images with magnification of ×40, ×, ×, respectively. a 1—3 Represented SHAM group with normal histopathologic assessment. Control group b 1—3 shows significant cyst formation, immune cell infiltration and vacuolization in the cord. Minocycline group c 1—3 elucidating significant vacuolization and minor cyst formation. Our results showed that in addition to significant improvement in behavioral responses, metformin substantially decreased histopathological signs of neuroinflammation and the level of TNF-α and IL-1β inflammatory cytokines in the cord tissue of spinal cord-injured rats. Interestingly, the therapeutic effects of metformin were similar to minocycline, a potential neuroprotective agent for SCI [ 5 , 13 ]. In the current study, tactile and heat stimulation tests were started a week after surgery when according to previous studies acute inflammation is reviled and regeneration is initiated [ 17 ]. Thus, these findings confirm that the applied treatments improved the pain threshold contrary to the expected course in SCI injured rodents. SCI leads to acute and chronic neuroinflammation associated with neurotoxicity, axonal damage and finally glial scarring. The scale of inflammation is directly associated with the release of inflammatory cytokines and also the amount of hemorrhage caused by SCI [ 20 , 21 ]. It is believed that cyst formation and glial scar, the most important inhibitors for neuroregeneration, are mostly formed by reactive astrocytes, macrophages and microglia [ 21 ]. The gradual increased inflammatory activation of these cells peaking 4 weeks after injury aggravates neuronal death and axonal damage. Inflammatory cytokines such as TNF-α and IL-1β are proposed to have a major role in this process [ 20 , 21 ]. Moreover, the post-SCI neuronal-glial interactions associated with maladaptive synaptic plasticity and cellular signaling and hyperactivity of sensory neurons contribute to the heightening of the neuropathic pain after SCI [ 22 ]. The histopathological evaluations in the current study showed that metformin and minocycline had similar effects on the spinal cord tissue, as they both significantly reduced inflammation, vacuolation, hemorrhage and cyst formation compared to the control group. The similar improvement of the functional behavior and reduced responsiveness to mechanical and thermal allodynia also verifies the hypothesized therapeutic effects of these treatments. Also, the similarity of our findings with previous studies on the efficacy of metformin and minocycline in SCI functional recovery could confirm the validity of these interventions[ 7 , 23 , 24 ]. These results are consistent with previous research showing that inhibition of proinflammatory cytokines has significant protective effects on neuronal death and axonal damage and improves healing in the regenerative process [ 21 ]. Studies have shown that microglial inhibition via neutralization of TNF-α and IL-1β attenuates neuropathic pain and mechanical hyperalgesia. Minocycline, described to be therapeutic in various pain facilitation studies, is considered to be an effective agent through inhibition of these cytokines, and thus reduced microglial activity [ 25 ]. Similar to the current research, investigations indicate that metformin inhibits these inflammatory cytokines e. In addition, regulation of autophagy by metformin promotes neuronal survival and functional recovery in spinal cord injury [ 7 ]. Likewise, minocycline inhibits inflammatory cytokines such as TNF-α. The attenuation of inflammatory cytokines by minocycline in addition to the anti-apoptotic properties of this agent are shown to have significant effect in SCI complications [ 13 , 28 , 29 ]. In the present study, the similar curative influence of metformin and minocycline in SCI-induced hyperalgesia, considering the akin significantly diminished histopathological impairment and proinflammatory TNF-α and IL-1β cytokines levels, promotes the hypothesis of an analogous protective interaction between these drugs. Recent researches have indicated that the normal inflammatory-regenerative sequence of tissue repair process is impaired in SCI [ 30 ]. It has been described that high levels of TNF-α lead to neurotoxicity, axonotomy and promotes inflammation [ 31 ]. The positive loop of cytokines generation leads to a continuous neurotoxicity and chronic inflammation, cessation of this vicious cycle, as shown by the results of the current study, would be beneficial for slowing and reversing the course of the impairment [ 30 , 32 ]. Multiple signaling pathways regulate the NF-κB levels, which have a major role in SCI inflammation and neurotoxicity, in cells affected by cord injury [ 33 , 34 ]. Some of these signaling pathways are the mitogen-activated protein kinase MAPK p38, the phosphoinositidekinase PI3K and mTOR [ 35 , 36 ]. It has been demonstrated that metformin as an inhibitor of mTOR attenuates neuronal damage and locomotor impairment, regulates autophagy and inhibits the NF-kappaB signaling [ 7 , 8 ]. Taken together, it could be suggested that inhibition of NF-kappaB signaling is a possible common pathway for the protective effect of metformin and minocycline. Although, as there are many cellular and pathological pathways in spinal cord injury, the exact evaluation of the protective mechanisms involved in treatment by these drugs were out of the scopes of the current research [ 38 , 39 ]. However, regarding the discussed similarities resulted from previous research and the current study, it could be concluded that metformin and minocycline attenuate the pathological and behavior outcomes of spinal cord injury through similar pathways with anti-inflammatory characteristics being prominent among them. However, the differences between these therapeutic approaches would be a noteworthy query. Significant weight loss is an acute characteristic of spinal cord injury, which occurs due to the metabolic changes, nutritional markers depletion and muscle atrophy [ 40 ]. Following the acute weight loss subjects suffering from immobility come into a weight gaining phase, which is mostly promoted by increased body fat and visceral adiposity that may lead to difficult challenges such as metabolic syndrome and cardiovascular complications [ 41 ]. In this study, minocycline significantly reversed the weight loss compared to control group. On the other hand, metformin administration was associated with significant weight loss. The contrast between the effects of these therapies could be implied by the fact that metformin is known to cause weight loss by lowering food intake through different pharmacological interactions such as improving insulin sensitivity and also improving lipid metabolism [ 42 ]. Considering the negative effects of weight gain in SCI, the weight losing characteristic of this drug, thus might be beneficial after cord injury. Indeed, more extensive studies with a focus on weight changes would be imperative for confirmation of these effects. According to this curve, the efficacy of metformin decreases at both very low and high doses [ 44 ]. In summary, we showed that metformin significantly improves locomotor activity and neuropathic pain in spinal cord-injured rodents through the attenuation of destructive neuroinflammatory responses. 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Download references. This study was financially supported by Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran Grant No and by a grant from the Iran National Science Foundation INSF. |
Mounting Metfformin suggests that Metformin and inflammation smooth muscle cells Types of lentils infammation Types of lentils involved in different inflammatory diseases that affect the bowel, Herbal metabolism regulator to altered morphology, contractility and augmented production of various Metformin and inflammation cytokines 1 inglammation, 2. Anx conducted using different animal models imflammation gastrointestinal diseases have demonstrated that growth and contractile properties of SMCs Infoammation substantially altered during mucosal Metformin and inflammation in Importance of healthy aging gastrointestinal tract due to increased expression Metdormin different cytokines inflmmation4. Patients who inflmmation from IBD experience symptoms associated with abnormal intestinal motility, resulting from abnormal proliferation and contractility of intestinal SMCs 3. Numerous studies have demonstrated that intestinal SMCs may produce different inflammatory mediators, including interleukin IL -6 and tumor necrosis factor-α TNF-α during various pathological conditions 25. Shi and Sarna 6 demonstrated that TNF-α binds to cognate receptors expressed on human CSMCs, resulting in activation of nuclear factor NF -κB and induction of expression of different cytokines and chemokines, including monocyte chemotactic protein MCP -1, IL-8 and intercellular adhesion molecule Furthermore, exposing human colonic C SMCs to different inflammatory stimuli led to enhanced expression of IL-1α, IL-6, IL-8, cyclooxygenase-2 and regulated on activation, normal T cell expressed and secreted RANTES 7. Ulcerative colitis and Crohn's disease are two distinct forms of IBD, affecting the colon and small intestine, respectively, and are characterized by chronic and relapsing intestinal inflammation 8.
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