Metformin . hydrochloride (CAS: 1115-70-4)

C₄H₁₁N₅ . HCl

• AMPK activator.
• Useful agent for immunometabolism research. Reported to stimulate AMP-activated protein kinase (AMPK), leading to the reduction in acetyl-CoA carboxylase (ACC) activity and induction of fatty acid oxidation. Mitochondrial electron transport chain complex I inhibitor, reducing mitochondrial reactive oxygen species (ROS).
• Antidiabetic and anti-hyperglycemic agent that reduces blood glucose levels, improves insulin sensitivity and decreases insulin resistance. Its metabolic effects, including the inhibition of hepatic gluconeogenesis, are mediated in part by activation of the LKB1-AMPK (AMP-activated protein kinase) pathway.
• Used as weight-loss agent in obesity and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD). Leptin sensitizer to mediate the weight-loss effect in the brain.
• Increases plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin's glucose-lowering effect.
• Anticancer agent with antiproliferative and proapoptotic activity in cancer cell lines.
• Autophagy activator.
• Activates the aPKC-CBP pathway in neural precursors to promote neurogenesis.
• Targets brown adipose tissue (BAT) in vivo and reduces oxygen consumption.

1. Role of AMP-activated protein kinase in mechanism of metformin action: G. Zhou, et al.; J. Clin. Invest. 108, 1167 (2001)
2. Enhanced secretion of glucagon-like peptide 1 by biguanide compounds: N. Yasuda, et al.; BBRC 298, 779 (2002)
3. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin: R.J. Shaw, et al.; Science 310, 1642 (2005)
4. AMP-activated protein kinase in metabolic control and insulin signalling: M.C. Towler & D.G. Hardie; Circ. Res. 100, 328 (2007)
5. Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation: J. Wang, et al.; Cell Stem Cell 11, 23 (2012)
6. Cellular and molecular mechanisms of metformin: An overview: B. Viollet, et al.; Clin. Sci. 122, 253 (2012)
7. Metformin in cancer: Translational challenges: R.J.O. Dowling, et al.; J. Mol. Endocrinol. 48, R31 (2012)
8. Metformin increases hepatic leptin receptor and decreases steatosis in mice: X. Tang, et al.; J. Endocrinol. 230, 227 (2016)
9. The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation: G.A. Gualdoni, et al. FASEB J. 30, 3800 (2016)
10. Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin: E. Bahne, et al.; Diabetes Obes. Metab. 18, 955 (2016) (Review)
11. A guide to immunometabolism for immunologists: L.A. O'Neill, et al.; Nat. Rev. Immunol. 16, 553 (2016)
12. The mechanisms of action of metformin: G. Rena, et al.; Diabetologia 60, 1577 (2017)
13. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles; L. Galluzzi, et al.; Nat. Rev. Drug. Discov.  16, 487 (2017)
14. Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro: P. Breining, et al.; Diabetes Obes. Metab. (Epub ahead of print) (2018)