diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/2072-0351-5582diaendo-6499Research ArticleСтатьиArticlesМетаболическая регуляция и цАМФ-зависимая протеинкиназа (АМРК): враг или союзник?Metabolicheskaya regulyatsiya i tsAMF-zavisimaya proteinkinaza (AMRK): vrag ili soyuznik?ЗалевскаяАлсу ГафуровнаZalevskayaAlsu Gafurovna-ПатракееваЕвгения МихайловнаPatrakeevaEvgenia Mikhailovna-Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова200815122008114№4 (2008)1217Copyright © Залевская А.Г., Патракеева Е.М., 20082008Залевская А.Г., Патракеева Е.М.Zalevskaya A.G., Patrakeeva E.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/6499

Общеизвестным фактом является высокая распро страненность и растущая частота сахарного диабета 2 типа (СД2), ожирения, сопутствующих им заболеваний. При всей очевидности терапевтических подходов, достижение целей лечения далеко не всегда успешно. Эти факты привели к необходимости углубления наших фундаментальных знаний о контроле энергетического гомеостаза.

цАМФ-зависимая протеинкиназагомеостазсахарный диабетReferencesein, S., et al. 2004. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care. 27:2067-2073.ein, S., et al. 2004. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care. 27:2067-2073.Wing, R.R., et al. 2001. Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity. Diabetes Care. 24:117-123.Wing, R.R., et al. 2001. Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity. Diabetes Care. 24:117-123.Hardie, D.G. 2004. The AMP-activated protein kinase pathway: new players upstream and downstream. J. Cell Sci. 117:5479-5487.Hardie, D.G. 2004. The AMP-activated protein kinase pathway: new players upstream and downstream. J. Cell Sci. 117:5479-5487.Kemp, B.E., et al. 2003. AMP-activated protein kinase, super metabolic regulator. Biochem. Soc. Trans. 31:162-168.Kemp, B.E., et al. 2003. AMP-activated protein kinase, super metabolic regulator. Biochem. Soc. Trans. 31:162-168.Carling, D. 2004. The AMP-activated protein kinase cascade: a unifying system for energy control. Trends Biochem. Sci. 29:18-24.Carling, D. 2004. The AMP-activated protein kinase cascade: a unifying system for energy control. Trends Biochem. Sci. 29:18-24.Hardie, D.G. 2003. Minireview. The AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology. 144:5179-5183.Hardie, D.G. 2003. Minireview. The AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology. 144:5179-5183.Hardie DG, Salt IP, Hawley SA, Davies SP 1999 AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J 338:717-722.Hardie DG, Salt IP, Hawley SA, Davies SP 1999 AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J 338:717-722.Hardie DG, Hawley SA 2001 AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays 23:1112-1119.Hardie DG, Hawley SA 2001 AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays 23:1112-1119.Birnbaum, M.J. 2005. Activating AMP-activated protein kinase without AMP. Mol. Cell. 19:289-290.Birnbaum, M.J. 2005. Activating AMP-activated protein kinase without AMP. Mol. Cell. 19:289-290.Hurley, R.L., et al. 2005. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J. Biol. Chem. 280:29060-29066.Hurley, R.L., et al. 2005. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J. Biol. Chem. 280:29060-29066.Fryer, L.G.D., Parbu-Patel, A., and Carling, D. 2002. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J. Biol. Chem. 277:25226-25232.Fryer, L.G.D., Parbu-Patel, A., and Carling, D. 2002. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J. Biol. Chem. 277:25226-25232.Corton, J.M., Gillespie, J.G., Hawley, S.A., and Hardie, D.G. 1995. 5- Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem. 229:558-565.Corton, J.M., Gillespie, J.G., Hawley, S.A., and Hardie, D.G. 1995. 5- Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem. 229:558-565.Longnus, S.L., Wambolt, R.B., Parsons, H.L., Brownsey, R.W., and Allard, M.F. 2003. 5-Aminoimidazole- 4-carboxamide 1-beta-D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284:R936-R944.Longnus, S.L., Wambolt, R.B., Parsons, H.L., Brownsey, R.W., and Allard, M.F. 2003. 5-Aminoimidazole- 4-carboxamide 1-beta-D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284:R936-R944.DeFronzo, R.A., Gunnarsson, R., Bjorkman, O., Olsson, M., and Wahren, J. 1985. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J. Clin. Invest. 76:149-155.DeFronzo, R.A., Gunnarsson, R., Bjorkman, O., Olsson, M., and Wahren, J. 1985. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J. Clin. Invest. 76:149-155.Hutber, C.A., Hardie, D.G., and Winder, W.W. 1997. Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase. Am. J. Physiol. Endocrinol. Metab. 272:E262-E266.Hutber, C.A., Hardie, D.G., and Winder, W.W. 1997. Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase. Am. J. Physiol. Endocrinol. Metab. 272:E262-E266.Merrill, G.F., Kurth, E.J., Hardie, D.G., and Winder, W.W. 1997. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am. J. Physiol. Endocrinol. Metab. 273:E1107-E1112.Merrill, G.F., Kurth, E.J., Hardie, D.G., and Winder, W.W. 1997. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am. J. Physiol. Endocrinol. Metab. 273:E1107-E1112.Kurth-Kraczek, E., Hirshman, M., Goodyear, L., and Winder, W. 1999. 5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes. 48:1667-1671.Kurth-Kraczek, E., Hirshman, M., Goodyear, L., and Winder, W. 1999. 5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes. 48:1667-1671.Barnes, B.R., et al. 2004. The 5 -AMP-activated protein kinase 3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J. Biol. Chem. 279:38441-38447.Barnes, B.R., et al. 2004. The 5 -AMP-activated protein kinase 3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J. Biol. Chem. 279:38441-38447.MacRae CA, Ghaisas N, Kass S, Donnelly S, Basson CT, Watkins HC, Anan R, Thierfelder LH, McGarry K, Rowland E et al. 1995. Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 96, 1216-1220.MacRae CA, Ghaisas N, Kass S, Donnelly S, Basson CT, Watkins HC, Anan R, Thierfelder LH, McGarry K, Rowland E et al. 1995. Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 96, 1216-1220.Tian R, Musi N, D'Agostino J, Hirshman MF & Goodyear LJ.2001. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation 104, 1664-1669.Tian R, Musi N, D'Agostino J, Hirshman MF & Goodyear LJ.2001. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation 104, 1664-1669.McLeod LE & Proud CG.2002. ATP depletion increases phosphorylation of elongation factor eEF2 in adult cardiomyocytes independently of inhibition of mTOR signalling. FEBS Lett 531, 448-452.McLeod LE & Proud CG.2002. ATP depletion increases phosphorylation of elongation factor eEF2 in adult cardiomyocytes independently of inhibition of mTOR signalling. FEBS Lett 531, 448-452.Horman S, Beauloye C, Vertommen D, Vanoverschelde JL, Hue L & Rider MH. 2003. Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2. J Biol Chem 278, 41970-41976.Horman S, Beauloye C, Vertommen D, Vanoverschelde JL, Hue L & Rider MH. 2003. Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2. J Biol Chem 278, 41970-41976.Browne GJ, Finn SG & Proud CG. 2004. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J Biol Chem 279, 12220-12231.Browne GJ, Finn SG & Proud CG. 2004. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J Biol Chem 279, 12220-12231.Browne GJ & Proud CG. 2004. A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol 24, 2986-2997.Browne GJ & Proud CG. 2004. A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol 24, 2986-2997.Chan AY, Soltys CL, Young ME, Proud CG & Dyck JR. 2004. Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem 279, 32771-32779.Chan AY, Soltys CL, Young ME, Proud CG & Dyck JR. 2004. Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem 279, 32771-32779.Saddik M, Gamble J,Witters LA & Lopaschuk GD. 1993 . Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. J Biol Chem 268, 25836-25845.Saddik M, Gamble J,Witters LA & Lopaschuk GD. 1993 . Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. J Biol Chem 268, 25836-25845.Thampy KG. 1989. Formation of malonyl coenzyme A in rat heart. Identification and purification of an isozyme of A carboxylase from rat heart. J Biol Chem 264, 17631-17634.Thampy KG. 1989. Formation of malonyl coenzyme A in rat heart. Identification and purification of an isozyme of A carboxylase from rat heart. J Biol Chem 264, 17631-17634.Dyck JR, Barr AJ, Barr RL, Kolattukudy PE & Lopaschuk GD . 1998. Characterization of cardiac malonyl-CoA decarboxylase and its putative role in regulating fatty acid oxidation. Am J Physiol 275, 2122-2129.Dyck JR, Barr AJ, Barr RL, Kolattukudy PE & Lopaschuk GD . 1998. Characterization of cardiac malonyl-CoA decarboxylase and its putative role in regulating fatty acid oxidation. Am J Physiol 275, 2122-2129.Russell RR 3rd, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ & Young LH 2004.AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction,apoptosis, and injury. J Clin Invest 114, 495-503.Russell RR 3rd, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ & Young LH 2004.AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction,apoptosis, and injury. J Clin Invest 114, 495-503.Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR 3rd & Young LH 2005. AMPactivated protein kinase activates p38 mitogenactivated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res 97, 872-879.Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR 3rd & Young LH 2005. AMPactivated protein kinase activates p38 mitogenactivated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res 97, 872-879.Meisse D, Van de Casteele M, Beauloye C, Hainault I, Kefas BA, Rider MH, Foufelle F & Hue L. 2002. Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells. FEBS Lett 526, 38-42.Meisse D, Van de Casteele M, Beauloye C, Hainault I, Kefas BA, Rider MH, Foufelle F & Hue L. 2002. Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells. FEBS Lett 526, 38-42.Kefas BA, Cai Y, Ling Z, Heimberg H, Hue L, Pipeleers D & Van de Casteele M. 2003. AMP-activated protein kinase can induce apoptosis of insulin-producing MIN6 cells through stimulation of c-Jun-N-terminal kinase. JMol Endocrinol 30, 151-161.Kefas BA, Cai Y, Ling Z, Heimberg H, Hue L, Pipeleers D & Van de Casteele M. 2003. AMP-activated protein kinase can induce apoptosis of insulin-producing MIN6 cells through stimulation of c-Jun-N-terminal kinase. JMol Endocrinol 30, 151-161.Igata M, Motoshima H, Tsuruzoe K, Kojima K, Matsumura T, Kondo T, Taguchi T, Nakamaru K, Yano M, Kukidome D, Matsumoto K, Toyonaga T, Asano T, Nishikawa T & Araki E . 2005. Adenosine monophosphateactivated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res 97, 837-844.Igata M, Motoshima H, Tsuruzoe K, Kojima K, Matsumura T, Kondo T, Taguchi T, Nakamaru K, Yano M, Kukidome D, Matsumoto K, Toyonaga T, Asano T, Nishikawa T & Araki E . 2005. Adenosine monophosphateactivated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res 97, 837-844.Hickson-Bick DL, Buja ML & McMillin JB. 2000. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. JMol Cell Cardiol 32, 511-519.Hickson-Bick DL, Buja ML & McMillin JB. 2000. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. JMol Cell Cardiol 32, 511-519.Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I &Watkins H. 2001. Mutations in the 2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 10, 1215-1220.Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I &Watkins H. 2001. Mutations in the 2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 10, 1215-1220.Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG & Seidman CE. 2002. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 109, 357-362.Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG & Seidman CE. 2002. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 109, 357-362.Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R & Hassan AS. 2001a. Identification of a gene responsible for familialWolff-Parkinson-White syndrome. N Engl JMed 344, 1823-1831.Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R & Hassan AS. 2001a. Identification of a gene responsible for familialWolff-Parkinson-White syndrome. N Engl JMed 344, 1823-1831.Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L & Roberts R. 2001b. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 104, 3030-3033.Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L & Roberts R. 2001b. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 104, 3030-3033.Gollob MH. 2003. Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. Biochem Soc Trans 31, 228-231.Gollob MH. 2003. Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. Biochem Soc Trans 31, 228-231.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. 2001. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167-1174.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. 2001. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167-1174.Yamagishi S., et al. Palmitat-induced apoptosis of microvascular endothelial cells and pericytes. Mol Med 2002; 8: 179-184Yamagishi S., et al. Palmitat-induced apoptosis of microvascular endothelial cells and pericytes. Mol Med 2002; 8: 179-184Li LX, et al. Induction of uncoupling protein 2 mRNA in beta-cells is stimulated by oxidation of FA but not by nutrient oversupply. Endocrinology. 2002; 143: 1371-1377Li LX, et al. Induction of uncoupling protein 2 mRNA in beta-cells is stimulated by oxidation of FA but not by nutrient oversupply. Endocrinology. 2002; 143: 1371-1377Bradley J. Davis, Zhonglin Xie, Benoit Viollet and Ming-Hui Zou. 2006. Activation of the AMP-Activated Kinase by Antidiabetes Drug Metformin Stimulates Nitric Oxide Synthesis In Vivo by Promoting the Association of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase. Diabetes 55:496-505.Bradley J. Davis, Zhonglin Xie, Benoit Viollet and Ming-Hui Zou. 2006. Activation of the AMP-Activated Kinase by Antidiabetes Drug Metformin Stimulates Nitric Oxide Synthesis In Vivo by Promoting the Association of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase. Diabetes 55:496-505.Derave, W., et al. 2000. Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle. Diabetes. 49:1281-1287.Derave, W., et al. 2000. Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle. Diabetes. 49:1281-1287.Mu, J., Brozinick, J.T., Jr., Valladares, O., Bucan, M., and Birnbaum, M.J. 2001. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol. Cell. 7:1085-1094.Mu, J., Brozinick, J.T., Jr., Valladares, O., Bucan, M., and Birnbaum, M.J. 2001. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol. Cell. 7:1085-1094.Barnes, B.R., et al. 2004. The 5 -AMP-activated protein kinase 3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J. Biol. Chem. 279:38441-38447.Barnes, B.R., et al. 2004. The 5 -AMP-activated protein kinase 3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J. Biol. Chem. 279:38441-38447.Musi, N., et al. 2002. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 51:2074-2081.Musi, N., et al. 2002. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 51:2074-2081.Kahn, B.B., Alquier, T., Carling, D., and Hardie, D.G. 2005. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1:15-25.Kahn, B.B., Alquier, T., Carling, D., and Hardie, D.G. 2005. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1:15-25.Zeigerer, A., McBrayer, M.K., and McGraw, T.E. 2004. Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160. Mol. Biol. Cell. 15:4406-4415.Zeigerer, A., McBrayer, M.K., and McGraw, T.E. 2004. Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160. Mol. Biol. Cell. 15:4406-4415.You M, Matsumoto M, Pacold CM, Cho WK & Crabb DW. 2004. The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127, 1798-1808.You M, Matsumoto M, Pacold CM, Cho WK & Crabb DW. 2004. The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127, 1798-1808.Peralta C, Bartrons R, Serafin A, Blazquez C, Guzman M, Prats N, Xaus C, Cutillas B, Gelpi E & Rosello-Catafau J 2001. Adenosine monophosphate- activated protein kinase mediates the protective effects of ischemic preconditioning on hepatic ischemia-reperfusion injury in the rat. Hepatology 34, 1164-1173.Peralta C, Bartrons R, Serafin A, Blazquez C, Guzman M, Prats N, Xaus C, Cutillas B, Gelpi E & Rosello-Catafau J 2001. Adenosine monophosphate- activated protein kinase mediates the protective effects of ischemic preconditioning on hepatic ischemia-reperfusion injury in the rat. Hepatology 34, 1164-1173.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. 2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8, 1288-1295.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. 2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8, 1288-1295.Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L & Scherer PE. 2006. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor agonists. J Biol Chem 281, 2654-2660.Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L & Scherer PE. 2006. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor agonists. J Biol Chem 281, 2654-2660.Benoit Viollet, Marc Foretz, Bruno Guigas, Sandrine Horman, Renaud Dentin, Luc Bertrand, Louis Hue and Fabrizio Andreelli. 2006. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J. Physiol. 574;41-53Benoit Viollet, Marc Foretz, Bruno Guigas, Sandrine Horman, Renaud Dentin, Luc Bertrand, Louis Hue and Fabrizio Andreelli. 2006. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J. Physiol. 574;41-53Rutter, G.A. 2001. Nutrient-secretion coupling in the pancreatic islet beta-cell: recent advances. Mol. Aspects Med. 22:247-284.Rutter, G.A. 2001. Nutrient-secretion coupling in the pancreatic islet beta-cell: recent advances. Mol. Aspects Med. 22:247-284.Salt, I.P., Johnson, G., Ashcroft, S.J., and Hardie, D.G. 1998. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate insulin release. Biochem. J. 335:533-539.Salt, I.P., Johnson, G., Ashcroft, S.J., and Hardie, D.G. 1998. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate insulin release. Biochem. J. 335:533-539.Zhang, S., and Kim, K.H. 1995. Glucose activation of acetyl-CoA carboxylase in association with insulin secretion in a pancreatic beta-cell line. J. Endocrinol.147:33-41.Zhang, S., and Kim, K.H. 1995. Glucose activation of acetyl-CoA carboxylase in association with insulin secretion in a pancreatic beta-cell line. J. Endocrinol.147:33-41.Kamohara, S., Burcelin, R., Halaas, J.L., Friedman, J.M., and Charron, M.J. 1997. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 389:374-377.Kamohara, S., Burcelin, R., Halaas, J.L., Friedman, J.M., and Charron, M.J. 1997. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 389:374-377.Haque, M., et al. 1999. Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes. 48:1706-1712.Haque, M., et al. 1999. Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes. 48:1706-1712.Tomas, E., et al. 2002. 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. U. S. A. 99:16309-16313.Tomas, E., et al. 2002. 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. U. S. A. 99:16309-16313.Minokoshi, Y., et al. 2004. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 428:569-574.Minokoshi, Y., et al. 2004. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 428:569-574.

The authors declare that there are no conflicts of interest present.