The role of AMP-activated protein kinase in obesity

Frontiers of Hormone Research

Volumn 36, Issue , 2007, Pages 198-211

  Kola, B ^a   Grossman, A ^a   Korbonits, M ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMP ACTIVATED PROTEIN KINASES; AMP-ACTIVATED PROTEIN KINASES; MULTIENZYME COMPLEX; PROTEIN SERINE THREONINE KINASE;

ADIPOSE TISSUE; ANIMAL; DISEASE MODEL; ENERGY METABOLISM; EXPERIMENTAL DIABETES MELLITUS; HUMAN; HYPOTHALAMUS; LIVER; METABOLISM; OBESITY; PANCREAS ISLET; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SKELETAL MUSCLE;

ADIPOSE TISSUE; ANIMALS; DIABETES MELLITUS, EXPERIMENTAL; DISEASE MODELS, ANIMAL; ENERGY METABOLISM; HUMANS; HYPOTHALAMUS; ISLETS OF LANGERHANS; LIVER; MULTIENZYME COMPLEXES; MUSCLE, SKELETAL; OBESITY; PROTEIN-SERINE-THREONINE KINASES;

EID: 43049096860     PISSN: 03013073     EISSN: None     Source Type: Book Series    
DOI: 10.1159/000115366     Document Type: Review

References (98)

1. Grundy SM, Hansen B, Smith SC Jr, Cleeman JI, Kahn RA: Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/ American Diabetes Association conference on scientific issues related to management. Circulation 2004;109:551-556.
2. Marx J: Cellular warriors at the battle of the bulge. Science 2003;299:846-849.
3. Xue B, Kahn BB: AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol (Lond) 2006;574:73-83.
4. Carling D: The AMP-activated protein kinase cascade-a unifying system for energy control. Trends Biochem Sci 2004;29:18-24.
5. Hardie DG, Hawley SA, Scott JW: AMP-activated protein kinase-development of the energy sensor concept. J Physiol (Lond) 2006;574:7-15.
6. Kahn BB, Alquier T, Carling D, Hardie DG: AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005;1:15-25.
7. Momcilovic M, Hong SP, Carlson M: Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J Biol Chem 2006;281:25336-25343.
8. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D: LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003;13:2004-2008.
9. Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, Frenguelli BG, Hardie DG: Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2005;2:9-19.
10. Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, Carlson M, Carling D: Ca2-+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2005;2:21-33.
11. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI: AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 2002;99:15983-15987.
12. DeFronzo RA, Gunnarsson R, Bjorkman O, Olsson M, Wahren J: Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J Clin Invest 1985;76:149-155.
13. Merrill GF, Kurth EJ, Hardie DG, Winder WW: AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 1997;273:E1107-E1112.
14. Iglesias MA, Ye JM, Frangioudakis G, Saha AK, Tomas E, Ruderman NB, Cooney GJ, Kraegen EW: AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 2002;51: 2886-2894.
15. Holmes BF, Sparling DP, Olson AL, Winder WW, Dohm GL: Regulation of muscle GLUT4 enhancer factor and myocyte enhancer factor 2 by AMP-activated protein kinase. Am J Physiol Endocrinol Metab 2005;289:E1071-E1076.
16. Oshel KM, Knight JB, Cao KT, Thai MV, Olson AL: Identification of a 30-base pair regulatory element and novel DNA binding protein that regulates the human GLUT4 promoter in transgenic mice. J Biol Chem 2000;275:23666-23673.
17. Buhl ES, Jessen N, Pold R, Ledet T, Flyvbjerg A, Pedersen SB, Pedersen O, Schmitz O, Lund S: Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes 2002;51:2199-2206.
18. Holmes BF, Kurth-Kraczek EJ, Winder WW: Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. J Appl Physiol 1999;87:1990-1995.
19. Carling D, Hardie DG: The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochim Biophys Acta 1989;1012:81-86.
20. Hardie DG, Sakamoto K: AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 2006;21:48-60.
21. Kelly M, Keller C, Avilucea PR, Keller P, Luo Z, Xiang X, Giralt M, Hidalgo J, Saha AK, Pedersen BK, Ruderman NB: AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun 2004;320:449-454.
22. Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ, Wackerhage H: Selective activation of AMPK-PGC-1 alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 2005;19:786-788.
23. Long YC, Zierath JR: AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest 2006;116:1776-1783.
24. Assifi MM, Suchankova G, Constant S, Prentki M, Saha AK, Ruderman NB: AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats. Am J Physiol Endocrinol Metab 2005;289:E794-E800.
25. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, Hue L, Andreelli F: Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol (Lond) 2006;574:41-53.
26. Daval M, Diot-Dupuy F, Bazin R, Hainault I, Viollet B, Vaulont S, Hajduch E, Ferre P, Foufelle F: Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. J Biol Chem 2005;280:25250-25257.
27. Daval M, Foufelle F, Ferre P: Functions of AMP-activated protein kinase in adipose tissue. J Physiol (Lond) 2006;574:55-62.
28. Orci L, Cook WS, Ravazzola M, Wang MY, Park BH, Montesano R, Unger RH: Rapid transformation of white adipocytes into fat-oxidizing machines. Proc Natl Acad Sci USA 2004;101:2058-2063.
29. Dagon Y, Avraham Y, Berry EM: AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2alpha in adipocytes. Biochem Biophys Res Commun 2006;340:43-47.
30. Yin W, Mu J, Birnbaum MJ: Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis in 3T3-L1 adipocytes. J Biol Chem 2003;278: 43074-43080.
31. Koh HJ, Hirshman MF, He H, Li Y, Manabe Y, Balschi JA, Goodyear LJ: Epinephrine is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes. Biochem J 2007.
32. Salt IP, Connell JM, Gould GW: 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes. Diabetes 2000;49:1649-1656.
33. Wu X, Motoshima H, Mahadev K, Stalker TJ, Scalia R, Goldstein BJ: Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 2003;52:1355-1363.
34. Gaidhu MP, Fediuc S, Ceddia RB: 5-Aminoimidazole-4-carboxamide-1-beta-D- ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes. J Biol Chem 2006;281:25956-25964.
35. Kola B, Boscaro M, Rutter GA, Grossman AB, Korbonits M: Expanding role of AMPK in endocrinology. Trends Endocrinol Metab 2006;17: 205-215.
36. Rutter GA, da SX, Leclerc I: Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem J 2003;375:1-16.
37. Kefas BA, Cai Y, Kerckhofs K, Ling Z, Martens G, Heimberg H, Pipeleers D, van de CM: Metformin-induced stimulation of AMP-activated protein kinase in beta-cells impairs their glucose responsiveness and can lead to apoptosis. Biochem Pharmacol 2004;68:409-416.
38. Richards SK, Parton LE, Leclerc I, Rutter GA, Smith RM: Over-expression of AMP-activated protein kinase impairs pancreatic {beta}-cell function in vivo. J Endocrinol 2005;187:225-235.
39. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB: AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 2004;428:569-574.
40. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ: Hypothalamic mTOR signaling regulates food intake. Science 2006;312:927-930.
41. Kahn BB, Myers MG Jr: mTOR tells the brain that the body is hungry. Nat Med 2006;12:615-617.
42. Mountjoy PD, Bailey SJ, Rutter GA: Inhibition by glucose or leptin of hypothalamic neurons expressing neuropeptide Y requires changes in AMP-activated protein kinase activity. Diabetologia 2007;50:168-177.
43. Martin TL, Alquier T, Asakura K, Furukawa N, Preitner F, Kahn BB: Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle. J Biol Chem 2006;281:18933-18941.
44. Steinberg GR, Watt MJ, Fam BC, Proietto J, Andrikopoulos S, Allen AM, Febbraio MA, Kemp BE: Ciliary neurotrophic factor suppresses hypothalamic AMP-kinase signaling in leptin-resistant obese mice. Endocrinology 2006;147:3906-3914.
45. Liu Y, Wan Q, Guan Q, Gao L, Zhao J: High-fat diet feeding impairs both the expression and activity of AMPKa in rats' skeletal muscle. Biochem Biophys Res Commun 2006;339:701-707.
46. Yu X, McCorkle S, Wang M, Lee Y, Li J, Saha AK, Unger RH, Ruderman NB: Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia 2004;47:2012-2021.
47. Tanaka T, Hidaka S, Masuzaki H, Yasue S, Minokoshi Y, Ebihara K, Chusho H, Ogawa Y, Toyoda T, Sato K, Miyanaga F, Fujimoto M, Tomita T, Kusakabe T, Kobayashi N, Tanioka H, Hayashi T, Hosoda K, Yoshimatsu H, Sakata T, Nakao K: Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification. Diabetes 2005;54: 2365-2374.
48. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, Thorens B, Vaulont S, Viollet B: 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;54:1331-1339.
49. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947-953.
50. Andreelli F, Foretz M, Knauf C, Cani PD, Perrin C, Iglesias MA, Pillot B, Bado A, Tronche F, Mithieux G, Vaulont S, Burcelin R, Viollet B: Liver adenosine monophosphate-activated kinase-alpha2 catalytic subunit is a key target for the control of hepatic glucose production by adiponectin and leptin but not insulin. Endocrinology 2006;147:2432-2441.
51. Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L, Scherer PE: Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 2006;281:2654-2660.
52. Steinberg GR, Smith AC, van Denderen BJ, Chen Z, Murthy S, Campbell DJ, Heigenhauser GJ, Dyck DJ, Kemp BE: AMP-activated protein kinase is not down-regulated in human skeletal muscle of obese females. J Clin Endocrinol Metab 2004;89:4575-4580.
53. Hojlund K, Mustard KJ, Staehr P, Hardie DG, Beck-Nielsen H, Richter EA, Wojtaszewski JF: AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes. Am J Physiol Endocrinol Metab 2004;286:E239-E244.
54. Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM: Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 2006;55:2277-2285.
55. Bluher M, Bullen JW Jr, Lee JH, Kralisch S, Fasshauer M, Kloting N, Niebauer J, Schon MR, Williams CJ, Mantzoros CS: Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. J Clin Endocrinol Metab 2006;91:2310-2316.
56. Roepstorff C, Thiele M, Hillig T, Pilegaard H, Richter EA, Wojtaszewski JF, Kiens B: Higher skeletal muscle alpha2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise. J Physiol (Lond) 2006;574:125-138.
57. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, Neufer PD: Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB J 2001;15:2748-2750.
58. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MA: Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 2006;55:2688-2697.
59. Dyck JR, Lopaschuk GD: AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol (Lond) 2006;574:95-112.
60. Chau-Van C, Gamba M, Salvi R, Gaillard RC, Pralong FP: Metformin inhibits adenosine 5′-monophosphate-activated kinase activation and prevents increases in neuropeptide y expression in cultured hypothalamic neurons. Endocrinology 2007;148:507-511.
61. Cai F, Gyulkhandanyan AV, Wheeler MB, Belsham DD: Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin. J Endocrinol 2007;192:605-614.
62. Zang M, Zuccollo A, Hou X, Nagata D, Walsh K, Herscovitz H, Brecher P, Ruderman NB, Cohen RA: AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells. J Biol Chem 2004;279:47898-47905.
63. Leclerc I, Woltersdorf WW, da SX, Rowe RL, Cross SE, Korbutt GS, Rajotte RV, Smith R, Rutter GA: Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab 2004;286:E1023-E1031.
64. Ravnskjaer K, Boergesen M, Dalgaard LT, Mandrup S: Glucose-induced repression of PPAR{alpha} gene expression in pancreatic {beta}-cells involves PP2A activation and AMPK inactivation. J Mol Endocrinol 2006;36:289-299.
65. Kovacic S, Soltys CL, Barr AJ, Shiojima I, Walsh K, Dyck JR: Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem 2003;278:39422-39427.
66. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, Carling D, Small CJ: AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 2004;279:12005-12008.
67. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002;415:339-343.
68. Steinberg GR, Rush JW, Dyck DJ: AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment. Am J Physiol Endocrinol Metab 2003;284:E648-E654.
69. Brabant G, Muller G, Horn R, Anderwald C, Roden M, Nave H: Hepatic leptin signaling in obesity. FASEB J 2005;19:1048-1050.
70. Uotani S, Abe T, Yamaguchi Y: Leptin activates AMP-activated protein kinase in hepatic cells via a JAK2-dependent pathway. Biochem Biophys Res Commun 2006;351:171-175.
71. Wang MY, Orci L, Ravazzola M, Unger RH: Fat storage in adipocytes requires inactivation of leptin's paracrine activity: implications for treatment of human obesity. Proc Natl Acad Sci USA 2005;102: 18011-18016.
72. Atkinson LL, Fischer MA, Lopaschuk GD: Leptin - activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis. J Biol Chem 2002;277:29424- 29430.
73. Russell RR, III, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ, Young LH: AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest 2004;114:495-503.
74. Kola B, Hubina E, Tucci SA, Kirkham TC, Garcia EA, Mitchell SE, Williams LM, Hawley SA, Hardie DG, Grossman AB, Korbonits M: Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem 2005;280:25196-25201.
75. Barazzoni R, Bosutti A, Stebel M, Cattin MR, Roder E, Visintin L, Cattin L, Biolo G, Zanetti M, Guarnieri G: Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle. Am J Physiol Endocrinol Metab 2005;288:E228-E235.
76. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8:1288-1295.
77. Tomas E, Tsao TS, Saha AK, Murrey HE, Zhang CC, Itani SI, Lodish HF, Ruderman NB: Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 2002;99:16309-16313.
78. Yoon MJ, Lee GY, Chung JJ, Ahn YH, Hong SH, Kim JB: Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes 2006;55:2562-2570.
79. Huypens P, Moens K, Heimberg H, Ling Z, Pipeleers D, van de CM: Adiponectin-mediated stimulation of AMP-activated protein kinase (AMPK) in pancreatic beta cells. Life Sci 2005;77:1273-1282.
80. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K: Adiponectin protects against myocardial ischemia-reperfusion injury through. Nat Med 2005;11: 1096-1103.
81. Liao Y, Takashima S, Maeda N, Ouchi N, Komamura K, Shimomura I, Hori M, Matsuzawa Y, Funahashi T, Kitakaze M: Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res 2005;67:705-713.
82. Palanivel R, Sweeney G: Regulation of fatty acid uptake and metabolism in L6 skeletal muscle cells by resistin. FEBS Lett 2005;579:5049-5054.
83. Muse ED, Obici S, Bhanot S, Monia BP, McKay RA, Rajala MW, Scherer PE, Rossetti L: Role of resistin in diet-induced hepatic insulin resistance. J Clin Invest 2004;114:232-239.
84. Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA: Regulation of fasted blood glucose by resistin. Science 2004;303:1195-1198.
85. Kimball SR, Siegfried BA, Jefferson LS: Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem 2004;279:54103-54109.
86. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE: Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-1174.
87. Huypens P, Quartier E, Pipeleers D, van de CM: Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase. Eur J Pharmacol 2005;518:90-95.
88. An D, Kewalramani G, Chan JK, Qi D, Ghosh S, Pulinilkunnil T, Abrahani A, Innis SM, Rodrigues B: Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3. Diabetologia 2006;49:2174-2184.
89. Fryer LG, Parbu-Patel A, Carling D: The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 2002;277:25226-25232.
90. Lessard SJ, Chen ZP, Watt MJ, Hashem M, Reid JJ, Febbraio MA, Kemp BE, Hawley JA: Chronic rosiglitazone treatment restores AMPK{alpha}2 activity in insulin-resistant rat skeletal muscle. Am J Physiol Endocrinol Metab 2006;290:E251-E257.
91. Bergeron R, Previs SF, Cline GW, Perret P, Russell RR III, Young LH, Shulman GI: Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 2001;50:1076-1082.
92. Sriwijitkamol A, Ivy JL, Christ-Roberts C, Defronzo RA, Mandarino LJ, Musi N: LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training. Am J Physiol Endocrinol Metab 2006;290:E925-E932.
93. Pold R, Jensen LS, Jessen N, Buhl ES, Schmitz O, Flyvbjerg A, Fujii N, Goodyear LJ, Gotfredsen CF, Brand CL, Lund S: Long-term AICAR administration and exercise prevents diabetes in ZDF rats. Diabetes 2005;54:928-934.
94. Halseth AE, Ensor NJ, White TA, Ross SA, Gulve EA: Acute and chronic treatment of ob/ob and db/db mice with AICAR decreases blood glucose concentrations. Biochem Biophys Res Commun 2002;294:798-805.
95. Ye JM, Dzamko N, Hoy AJ, Iglesias MA, Kemp B, Kraegen E: Rosiglitazone treatment enhances acute AMP-activated protein kinase-mediated muscle and adipose tissue glucose uptake in high-fat-fed rats. Diabetes 2006;55:2797-2804.
96. Giri S, Rattan R, Haq E, Khan M, Yasmin R, Won JS, Key L, Singh AK, Singh I: AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model. Nutr Metab (Lond) 2006;3:31.
97. Motoshima H, Goldstein BJ, Igata M, Araki E: AMPK and cell proliferation-AMPK as a therapeutic target for atherosclerosis and cancer. J Physiol (Lond) 2006;574:63-71.
98. Du M, Shen QW, Zhu MJ, Ford SP: Leucine stimulates mTOR signalling in C2C12 myoblasts in part through inhibition of AMP-activated protein kinase. J Anim Sci 2006;919-927.