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Function and therapeutic potential of metformin in multiple diseases
  • wei mu
wei mu
Central Military Commission Joint Logistics Support Force 904th Hospital

Corresponding Author:[email protected]

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Abstract

Metformin is one of the first-line and widely-used drugs in patients with T2DM due to its safety profile, clinical efficacy and cheap cost. It is clearly that metformin has benefits on lowering hyperglycemia and diabetes-related complications in clinical use. However, the exact mechanisms of metformin in multiple therapies are still blurred. The classic effect of metformin is to reduce hepatic glucose production by inhibiting gluconeogenesis in liver and increase glucose utilization in peripheral tissues. Metformin targets mitochondrial respiratory chain complex I to specifically reduce reactive oxygen species generation to protect cells against oxidative stress-induced cell apoptosis. AMPK complex is a key factor in the action of metformin; however it is inconclusive that metformin activate AMPK directly or indirectly. Furthermore, the liver-centered mechanism of metformin has been challenged by that of gut microbiota alteration and GLP-1 secretion. Actually, more and more studies showed that metformin act on gut microbiota to exert anti-hyperglycemia effect. In addition, new emerging evidence showed that metformin has off-label function on bone metabolism, cancer inhibition and lifespan extension; however the underlying mechanism of such properties of metformin still remains elusive. Despite most of results are from cells in vitro and model organisms, clinical trials have been recruited by institutes around the world to verify the therapeutic effects of metformin in anti-tumor and anti-aging. Taken together, in this review we provide a new perspective on metformin and repurpose its novel and promising application in the therapy of cancer, bone fracture healing and age-related diseases.