An energetic tale of AMPK-independent effects of metformin

Journal of Clinical Investigation

Volumn 120, Issue 7, 2010, Pages 2267-2270

  Miller, Russell A ^a   Birnbaum, Morris J ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE PHOSPHATE; ADENOSINE TRIPHOSPHATE; ADENYLATE KINASE; GLUCAGON; INSULIN; METFORMIN; PHENFORMIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); ANTIDIABETIC AGENT; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PROTEIN KINASE;

DRUG MECHANISM; ENERGY TRANSFER; GALEGA; GENE EXPRESSION; GLUCONEOGENESIS; GLUCOSE TRANSPORT; GLYCOLYSIS; HORMONAL REGULATION; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NOTE; OBESITY; PRIORITY JOURNAL; CARBOHYDRATE METABOLISM; DRUG EFFECT; LIVER; LIVER CELL; METABOLISM; SIGNAL TRANSDUCTION;

AMP-ACTIVATED PROTEIN KINASES; CARBOHYDRATE METABOLISM; DIABETES MELLITUS, TYPE 2; GENE EXPRESSION; HEPATOCYTES; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; LIVER; METFORMIN; PROTEIN KINASES; SIGNAL TRANSDUCTION;

EID: 77954964776     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI43661     Document Type: Note

References (25)

1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21(9):1414-1431.
2. Bosi E. Metformin - the gold standard in type 2 diabetes: what does the evidence tell us? Diabetes Obes Metab. 2009;11(suppl 2):3-8.
3. Nathan DM, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203.
4. Watanabe C. Studies in the metabolic changes induced by administration of guanidine bases. I. Influence of injected guanidine hydrochloride upon blood sugar content. J Biol Chem. 1918;33:253-265.
5. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care. 1989;12(8):553-564. (Pubitemid 19214828)
6. Goodarzi MO, Bryer-Ash M. Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Diabetes Obes Metab. 2005;7(6):654-665. (Pubitemid 41601070)
7. Ferner RE, Rawlins MD, Alberti KG. Impaired betacell responses improve when fasting blood glucose concentration is reduced in non-insulin-dependent diabetes. Q J Med. 1988;66(250):137-146.
8. Selvin E, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008;168(19):2070-2080.
9. El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000;275(1):223-228. (Pubitemid 30038975)
10. Zhou G, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108(8):1167-1174.
11. Foretz M, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes. 2005;54(5):1331-1339. (Pubitemid 40586661)
12. Foretz M, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/ AMPK pathway via a decrease in hepatic energy state. J Clin Invest. 2010;120(7):2355-2369.
13. Berglund ED, et al. Hepatic energy state is regulated by glucagon receptor signaling in mice. J Clin Invest. 2009;119(8):2412-2422.
14. Tanaka T, Sue F, Morimura H. Feed-forward activation and feed-back inhibition of pyruvate kinase type L of rat liver. Biochem Biophys Res Commun. 1967;29(3):444-449.
15. Kemp RG. Rabbit liver phosphofructokinase. Comparison of some properties with those of muscle phosphofructokinase. J Biol Chem. 1971;246(1):245-252.
16. Van Schaftingen E, Hers HG. Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-biphosphate. Proc Natl Acad Sci U S A. 1981;78(5):2861-2863.
17. Taylor SI, Mukherjee C, Jungas RL. Regulation of pyruvate dehydrogenase in isolated rat liver mitochondria. Effects of octanoate, oxidationreduction state, and adenosine triphosphate to adenosine diphosphate ratio. J Biol Chem. 1975;250(6):2028-2035.
18. Burgess SC, et al. Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab. 2007;5(4):313-320.
19. Samuel VT, et al. Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with type 2 diabetes. Proc Natl Acad Sci U S A. 2009;106(29):12121-12126.
20. Shaw RJ, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310(5754):1642-1646.
21. He L, et al. Metformin and insulin suppress hepat ic gluconeogenes i s through phos - phorylation of CREB binding protein. Cell. 2009;137(4):635-646.
22. Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell. 2001;7(5):1085-1094. (Pubitemid 32525754)
23. Musi N, Hayashi T, Fujii N, Hirshman MF, Witters LA, Goodyear LJ. AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle. Am J Physiol Endocrinol Metab. 2001;280(5):E677-E684. (Pubitemid 32466834)
24. Kalender A, et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010;11(5):390-401.
25. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32(9):1620-1625.