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Metformin

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Metformin

Description

Metformin is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I.


Reference: Brunmair 2004 Diabetes

Metformin and mitObesity

Work in progress by Gnaiger E 2020-02-10 linked to a preprint in preparation on BME and mitObesity.

References: Metformin

  1. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhäusl W, Fürnsinn C (2004) Thiazolidinediones, like metformin, inhibit respiratory Complex I: a common mechanism contributing to their antidiabetic actions?. Diabetes 53:1052-9. - »Bioblast link«
  2. Dantas-Ferreira RF, Raingard H, Dumont S, Schuster-Klein C, Guardiola-Lemaitre B, Pevet P, Challet E (2018) Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high-fat-fed rats. Endocrinol Diabetes Metab 1:e00039. - https://www.ncbi.nlm.nih.gov/pubmed/30815567
  3. Alshahrani A, AlDubayee M, Zahra M, Alsebayel FM, Alammari N, Alsudairy F, Almajed M, Aljada A (2019) Differential expression of human N-alpha-acetyltransferase 40 (hNAA40), nicotinamide phosphoribosyltransferase (NAMPT) and Sirtuin-1 (SIRT-1) pathway in obesity and T2DM: modulation by metformin and macronutrient intake. Diabetes Metab Syndr Obes 12:2765-74. - https://www.ncbi.nlm.nih.gov/pubmed/31920356
  4. Sanches-Silva A, Testai L, Nabavi SF, Battino M, Devi KP, Tejada S, Sureda A, Xu S, Yousefi B, Majidinia M, Russo GL, Efferth T, Nabavi SM, Farzaei MH (2020) Therapeutic potential of polyphenols in cardiovascular diseases: regulation of mTOR signaling pathway. Pharmacol Res 2020 Jan 2:104626. - https://www.ncbi.nlm.nih.gov/pubmed/31904507
  5. Srivastava SB (2019) Is there a prescription to treat pediatric obesity? Am J Lifestyle Med 14:36-9. - https://www.ncbi.nlm.nih.gov/pubmed/31903078
  6. McCrimmon RJ, Catarig AM, Frias JP, Lausvig NL, le Roux CW, Thielke D, Lingvay I (2020) Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. Diabetologia 2020 Jan 2. doi: 10.1007/s00125-019-05065-8. - https://www.ncbi.nlm.nih.gov/pubmed/31897524
  7. Kothari S, Dhami-Shah H, Shah SR (2019) Antidiabetic drugs and statins in nonalcoholic fatty liver disease. J Clin Exp Hepatol 9:723-30. - https://www.ncbi.nlm.nih.gov/pubmed/31889754
  8. Hiluy JC, Nazar BP, Gonçalves WS, Coutinho W, Appolinario JC (2019) Effectiveness of pharmacologic interventions in the management of weight gain in patients with severe mental illness: a systematic review and meta-analysis. Prim Care Companion CNS Disord 21 pii: 19r02483. - https://www.ncbi.nlm.nih.gov/pubmed/31856432
  9. Crocker CL, Baumgarner BL, Kinsey ST (2019) β-guanidinopropionic acid and metformin differentially impact autophagy, mitochondria and cellular morphology in developing C2C12 muscle cells. J Muscle Res Cell Motil. 2019 Dec 13. doi: 10.1007/s10974-019-09568-0. - https://www.ncbi.nlm.nih.gov/pubmed/31836952
  10. Guo H, Kong W, Zhang L, Han J, Clark LH, Yin Y, Fang Z, Sun W, Wang J, Gilliam TP, Lee D, Makowski L, Zhou C, Bae-Jump VL (2019) Reversal of obesity-driven aggressiveness of endometrial cancer by metformin. Am J Cancer Res 9:2170-93. - https://www.ncbi.nlm.nih.gov/pubmed/31720081
  11. Wang Y, An H, Liu T, Qin C, Sesaki H, Guo S, Radovick S, Hussain M, Maheshwari A, Wondisford FE, O'Rourke B, He L (2019) Metformin improves mitochondrial respiratory activity through activation of AMPK. Cell Rep 29:1511-23.e5. - https://www.ncbi.nlm.nih.gov/pubmed/31693892
  12. MacNeil LT, Schertzer JD, Steinberg GR (2020) Bacteria transmit metformin-associated lifespan extension. Nat Rev Endocrinol 16:9-10. - https://www.ncbi.nlm.nih.gov/pubmed/31645681
  13. El-Sayed SM, Ibrahim HM (2019) Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy. Folia Morphol (Warsz). 2019 Sep 6. doi: 10.5603/FM.a2019.0100. - https://www.ncbi.nlm.nih.gov/pubmed/31489607
  14. Hartman SJ, Nelson SH, Marinac CR, Natarajan L, Parker BA, Patterson RE (2019) The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study. Psychooncology 28:1640-46. - https://www.ncbi.nlm.nih.gov/pubmed/31140202
  15. Rotermund C, Machetanz G, Fitzgerald JC (2018) The therapeutic potential of metformin in neurodegenerative diseases. Front Endocrinol (Lausanne) 9:400. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060268/
  16. Glossmann HH, Lutz OMD (2019) Metformin and aging: a review. Gerontology 65:581-90. - https://www.karger.com/Article/FullText/502257#
  17. Saraei P, Asadi I, Kakar MA, Moradi-Kor N (2019) The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag Res 11:3295-313. - https://www.ncbi.nlm.nih.gov/pubmed/31114366
  18. Higgins L, Palee S, Chattipakorn SC, Chattipakorn N (2019) Effects of metformin on the heart with ischaemia-reperfusion injury: Evidence of its benefits from in vitro, in vivo and clinical reports. Eur J Pharmacol 858:172489. - https://www.sciencedirect.com/science/article/pii/S0014299919304418
  19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654524/
  20. https://www.ncbi.nlm.nih.gov/pubmed/30151735
  21. https://journals.lww.com/jhypertension/Abstract/2017/01000/Effects_of_metformin_on_blood_pressure_in.4.aspx
  22. https://pubmed.ncbi.nlm.nih.gov/28208582-nutrients-in-energy-and-one-carbon-metabolism-learning-from-metformin-users/?from_term=Obesity+and+comorbidities+and+mitochondria&from_page=4&from_pos=1

MitoPedia: mitObesity drugs

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TermAbbreviationDescription
AspirinAspirin is a widely applied drug that requires dosage adjusted to individual body mass. It is a non-selective COX inhibitor and exerts an effect on long-chain fatty acid transport into mitochondria.
CurcuminCurcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. The protective effects of curcumin on rat heart mitochondrial injuries induced by in vitro anoxia–reoxygenation were evaluated by Xu et al 2013. It was found that curcumin added before anoxia or immediately prior to reoxygenation exhibited remarkable protective effects against anoxia–reoxygenation induced oxidative damage to mitochondria.
ElamipretideBendaviaBendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.
FlavonoidsFlavonoids are a group of bioactive polyphenols with potential antioxidant and anti-inflammatory effects, abundant in fruits and vegetables, and in some medicinal herbs. Flavonoids are synthesized in plants from phenylalanine. Dietary intake of flavonoids as nutraceuticals is discussed for targeting T2D and other degenerative diseases.
MelatoninaMTMelatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article
MetforminMetformin (dimethylbiguanide) is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I and glycerophosphate dehydrogenase complex.
RapamycinRapamycin is an inhibitor of the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). Rapamycin induces autophagy and dyscouples mitochondrial respiration. Rapamycin delays senescence in human cells, and extends lifespan in mice without detrimental effects on mitochondrial fitness in skeletal muscle.
ResveratrolResveratrol is a natural bioactive phenol prouced by several plants with antioxidant and anti-inflammatory effects. Dietary intake as nutraceutical is discussed for targeting mitochondria with a wide spectrum of action in degenerative diseases.
SpermidineSpermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.
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 Healthy reference population     Body mass excess         BFE         BME cutoffs         BMI         H         M         VO2max         mitObesity drugs



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