- Reaven, G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988). Classic reference describing what is now referred to as the metabolic or insulin resistance syndrome.
CAS PubMed Google Scholar
- Ruderman, N., Chisholm, D., Pi-Sunyer, X. & Schneider, S. The metabolically obese, normal-weight individual revisited. Diabetes 47, 699–713 (1998).
CAS PubMed Google Scholar
- Reaven, G. Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease. Circulation 106, 286–288 (2002).
Article PubMed Google Scholar
- Kissebah, A. H. et al. Relation of body fat distribution to metabolic complications of obesity. J. Clin. Endocrinol. Metab. 54, 254–260 (1982).
CAS PubMed Google Scholar
- Nyholm, B. et al. Insulin resistance in relatives of NIDDM patients: the role of physical fitness and muscle metabolism. Diabetologia 39, 813–822 (1996).
CAS PubMed Google Scholar
- Ruderman, N. B., Saha, A. K., Vavvas, D. & Witters, L. A. Malonyl-CoA, fuel sensing, and insulin resistance. Am. J. Physiol. 276, E1–E18 (1999). Review describing early work that led to the concept of a malonyl CoA fuel sensing and signaling mechanism, its regulation by AMPK and the possible contribution of its dysregulation to insulin resistance and obesity.
CAS PubMed Google Scholar
- McGarry, J. D. Banting lecture 2001: Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51, 7–18 (2002).
CAS PubMed Google Scholar
- Unger, R. H. Lipotoxic diseases. Annu. Rev. Med. 53, 319–336 (2002). Excellent review of the concept of lipotoxicity and its contribution to type 2 diabetes and other disorders associated with the metabolic syndrome.
CAS PubMed Google Scholar
- Prentki, M. & Corkey, B. E. Are the β-cell signaling molecules malonyl-CoA and cystolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes 45, 273–283 (1996). Early review of malonyl CoA and long chain acyl-CoA regulation in the pancreatic β-cell and the implication of such regulation to cellular dysfunction in other tissues.
CAS PubMed Google Scholar
- Ryysy, L. et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 49, 749–758 (2000).
CAS PubMed Google Scholar
- Krssak, M. et al. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 42, 113–116 (1999).
CAS PubMed Google Scholar
- Jacob, S. et al. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes 48, 1113–1119 (1999).
CAS PubMed Google Scholar
- Seppala-Lindroos, A. et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J. Clin. Endocrinol. Metab. 87, 3023–3028 (2002).
CAS PubMed Google Scholar
- Lee, Y. et al. β-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-β-cell relationships. Proc. Natl Acad. Sci. USA 91, 10878–10882 (1994).
CAS PubMed PubMed Central Google Scholar
- Ohneda, M., Inman, L. R. & Unger, R. H. Caloric restriction in obese pre-diabetic rats prevents β-cell depletion, loss of β-cell GLUT 2 and glucose incompetence. Diabetologia 38, 173–179 (1995).
CAS PubMed Google Scholar
- Higa, M. et al. Troglitazone prevents mitochondrial alterations, β-cell destruction, and diabetes in obese prediabetic rats. Proc. Natl Acad. Sci. USA 96, 11513–11518 (1999).
CAS PubMed PubMed Central Google Scholar
- Unger, R. H. & Orci, L. Diseases of liporegulation: new perspective on obesity and related disorders. FASEB J. 15, 312–321 (2001).
CAS PubMed Google Scholar
- Ruderman, N. B. et al. Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem. Soc. Trans. 31, 202–206 (2003). Review of earlier work linking dysregulation of malonyl-CoA and AMPK to insulin resistance in muscle and dysfunction in the endothelial cell.
CAS PubMed Google Scholar
- Prentki, M. J. E., El-Assaad W, Roduit, R. Malonyl-CoA Signaling, Lipid Partitioning, and Glucolipotoxicity: Role in β-cell adaptation and failure in the etiology of diabetes. Diabetes 51, S405–S413 (2002).
CAS PubMed Google Scholar
- Listenberger, L. L. et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl Acad. Sci. USA 100, 3077–3082 (2003).
CAS PubMed PubMed Central Google Scholar
- McGarry, J. D. & Brown, N. F. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur. J. Biochem. 244, 1–14 (1997). Review of carnitine palmitoyl transferase regulation and its significance by the investigator who first demonstrated its inhibition by malonyl-CoA.
CAS PubMed Google Scholar
- Prentki, M. & Matschinsky, F. M. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol. Rev. 67, 1185–1248 (1987).
CAS PubMed Google Scholar
- Corkey, B. E. et al. A role for malonyl-CoA in glucose-stimulated insulin secretion from clonal pancreatic β-cells. J. Biol. Chem. 264, 21608–21612 (1989). Initial paper suggesting a relationship between malonyl-CoA and glucose stimulated insulin secretion by the pancreatic β-cell.
CAS PubMed Google Scholar
- Prentki, M. et al. Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J. Biol. Chem. 267, 5802–5810 (1992).
CAS PubMed Google Scholar
- Saha, A. K., Kurowski, T. G. & Ruderman, N. B. A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation. Am. J. Physiol. 269, E283–E289 (1995).
CAS PubMed Google Scholar
- Saha, A. K., Kurowski, T. G., Colca, J. R. & Ruderman, N. B. Lipid abnormalities in tissues of the KKAy mouse: effects of pioglitazone on malonyl-CoA and diacylglycerol. Am. J. Physiol. 267, E95–E101 (1994).
CAS PubMed Google Scholar
- Hu, Z., Cha, S. H., Chohnan, S. & Lane, M. D. Hypothalamic malonyl-CoA as a mediator of feeding behavior. Proc. Natl Acad. Sci. USA 100, 12624–12629 (2003).
CAS PubMed PubMed Central Google Scholar
- Hardie, D. G. & Carling, D. The AMP-activated protein kinase — fuel gauge of the mammalian cell? Eur. J. Biochem. 246, 259–273 (1997). Important review by the co-discovers of AMPK, 10 years after they first identified the enzyme.
CAS PubMed Google Scholar
- Kemp, B. E. et al. AMP-activated protein kinase, super metabolic regulator. Biochem. Soc. Trans. 31, 162–168 (2003). Thoughtful review by a leading investigator in the AMPK field summarizing his plenary lecture at the Second International AMPK Symposium.
CAS PubMed Google Scholar
- Dagher, Z., Ruderman, N., Tornheim, K. & Ido, Y. Acute regulation of fatty acid oxidation and AMP-activated protein kinase in human umbilical vein endothelial cells. Circ. Res. 88, 1276–1282 (2001). Initial demonstration that the AMPK/malonyl-CoA fuel-sensing and signalling network operates in endothelium.
CAS PubMed Google Scholar
- Itani, S. I. et al. Glucose autoregulates its uptake in skeletal muscle: involvement of AMP-activated protein kinase. Diabetes 52, 1635–1640 (2003).
CAS PubMed Google Scholar
- Fryer, L. G., Parbu-Patel, A. & Carling, D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J. Biol. Chem. 277, 25226–25232 (2002).
CAS PubMed Google Scholar
- Hawley, S. A., Gadalla, A. E., Olsen, G. S. & Hardie, D. G. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51, 2420–2425 (2002).
CAS PubMed Google Scholar
- Woods, A. et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 13, 2004–2008 (2003).
CAS PubMed Google Scholar
- Saha, A. K. et al. Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside. J. Biol. Chem. 275, 24279–24283 (2000).
CAS PubMed Google Scholar
- Muoio, D. M., Seefeld, K., Witters, L. A. & Coleman, R. A. AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem. J. 338, 783–791 (1999).
CAS PubMed PubMed Central Google Scholar
- Ferre, P., Azzout-Marniche, D. & Foufelle, F. AMP-activated protein kinase and hepatic genes involved in glucose metabolism. Biochem. Soc. Trans. 31, 220–223 (2003).
CAS PubMed Google Scholar
- Winder, W. W. et al. Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J. Appl. Physiol. 88, 2219–2226 (2000).
CAS PubMed Google Scholar
- Rutter, G. A., DaSilvaXavier, G. & Leclerc, I. Roles of 5′AMP-activated protein kinase in mammalian glucose homeostasis. Biochem. J. 375, 1–16 (2003).
CAS PubMed PubMed Central Google Scholar
- Zhou, M., Lin, B. Z., Coughlin, S., Vallega, G. & Pilch, P. F. UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase. Am. J. Physiol. Endocrinol. Metab. 279, E622–E629 (2000).
CAS PubMed Google Scholar
- Pedersen, S. B., Lund, S., Buhl, E. S. & Richelsen, B. Insulin and contraction directly stimulate UCP2 and UCP3 mRNA expression in rat skeletal muscle in vitro. Biochem. Biophys. Res. Commun. 283, 19–25 (2001).
CAS PubMed Google Scholar
- Zheng, D. et al. Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. J. Appl. Physiol. 91, 1073–1083 (2001).
CAS PubMed Google Scholar
- Leff, T. AMP-activated protein kinase regulates gene expression by direct phosphorylation of nuclear proteins. Biochem. Soc. Trans. 31, 224–247 (2003).
CAS PubMed Google Scholar
- Barthels, A., Schmoll, D., Kruger, K. D., Roth, R. A. & Joost, H. G. Regulation of the forkhead transcription factor FKHR (FOXO1a) by glucose starvation and AICAR, an activator of AMP-activated protein kinase. Endocrinology 143, 3183–3186 (2002).
Google Scholar
- Leclerc, I. et al. Hepatocyte nuclear factor-4α involved in type 1 maturity-onset diabetes of the young is a novel target of AMP-activated protein kinase. Diabetes 50, 1515–1521 (2001).
CAS PubMed Google Scholar
- Terada, S. et al. Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem. Biophys. Res. Commun. 296, 350–354 (2002).
CAS PubMed Google Scholar
- Suwa, M., Nakano, H. & Kumagai, S. Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles. J. Appl. Physiol. 95, 960–968 (2003).
CAS PubMed Google Scholar
- Randle, P., Garland, P. B., Hales, C. N. & Newsholme, E. A. The glucose fatty-acid cycyel its role in insulin sensitivity and the metabolic disturbance of diabetes mellitus. Lancet 1, 785–789 (1963).
CAS PubMed Google Scholar
- Randle, P. J. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab. Rev. 14, 263–283 (1998).
CAS PubMed Google Scholar
- Boden, G. et al. Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. J. Clin. Invest. 88, 960–966 (1991). Historically important paper showing that fatty acids produce insulin resistance in human muscle and that they do so by a mechanism other than the glucose-fatty acid cycle of Randle.
CAS PubMed PubMed Central Google Scholar
- Heydrick, S. J., Ruderman, N. B., Kurowski, T. G., Adams, H. B. & Chen, K. S. Enhanced stimulation of diacylglycerol and lipid synthesis by insulin in denervated muscle. Altered protein kinase C activity and possible link to insulin resistance. Diabetes 40, 1707–1711 (1991). Early paper linking insulin resistance in skeletal muscle to altered cellular lipid metabolism, increased DAG mass and protein kinase C activation.
CAS PubMed Google Scholar
- Lin, Y. et al. Alterations of nPKC distribution, but normal Akt/PKB activation in denervated rat soleus muscle. Am. J. Physiol. Endocrinol. Metab. 283, E318–E325 (2002).
CAS PubMed Google Scholar
- Considine, R. V. et al. Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia. J. Clin. Invest. 95, 2938–2944 (1995).
CAS PubMed PubMed Central Google Scholar
- Itani, S. I., Ruderman, N. B., Schmieder, F. & Boden, G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκBα. Diabetes 51, 2005–2011 (2002).
CAS PubMed Google Scholar
- Shulman, G. I. Cellular mechanisms of insulin resistance. J. Clin. Invest. 106, 171–176 (2000).
CAS PubMed PubMed Central Google Scholar
- Yuan, M. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ. Science 293, 1673–1677 (2001).
CAS PubMed Google Scholar
- Hundal, R. S. et al. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J. Clin. Invest. 109, 1321–1326 (2002).
CAS PubMed PubMed Central Google Scholar
- Goodpaster, B. H., He, J., Watkins, S. & Kelley, D. E. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab. 86, 5755–5761 (2001).
CAS PubMed Google Scholar
- Kraegen, E. W. et al. Insulin resistance induced by glucose infusion is associated temporally with reduced muscle and liver AMPK activity. Diabetes 52, A330 (2003).
Google Scholar
- Laybutt, D. R. et al. Muscle lipid accumulation and protein kinase C activation in the insulin-resistant chronically glucose-infused rat. Am. J. Physiol. 277, E1070–E1076 (1999).
CAS PubMed Google Scholar
- Iglesias, M. A. et al. AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 51, 2886–2894 (2002).
CAS PubMed Google Scholar
- Oakes, N. D. et al. Diet-induced muscle insulin resistance in rats is ameliorated by acute dietary lipid withdrawal or a single bout of exercise: parallel relationship between insulin stimulation of glucose uptake and suppression of long-chain fatty acyl-CoA. Diabetes 46, 2022–2028 (1997).
CAS PubMed Google Scholar
- Mu, J., Brozinick, J. T., Jr., Valladares, O., Bucan, M. & Birnbaum, M. J. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol. Cell 7, 1085–1094 (2001).
CAS PubMed Google Scholar
- Viollet, B. et al. The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity. J. Clin. Invest. 111, 91–98 (2003).
CAS PubMed PubMed Central Google Scholar
- Lingohr, M. K., Buettner, R. & Rhodes, C. J. Pancreatic β-cell growth and survival — a role in obesity-linked type 2 diabetes? Trends Mol. Med. 8, 375–384 (2002).
CAS PubMed Google Scholar
- Poitout, V. & Robertson, R. P. Minireview: Secondary β-cell failure in type 2 diabetes — a convergence of glucotoxicity and lipotoxicity. Endocrinology 143, 339–342 (2002).
CAS PubMed Google Scholar
- Porte, D., Jr. Banting lecture 1990. β-cells in type II diabetes mellitus. Diabetes 40, 166–180 (1991).
PubMed Google Scholar
- Pick, A. et al. Role of apoptosis in failure of β-cell mass compensation for insulin resistance and β-cell defects in the male Zucker diabetic fatty rat. Diabetes 47, 358–364 (1998).
CAS PubMed Google Scholar
- Butler, A. E. et al. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 52, 102–110 (2003).
CAS PubMed Google Scholar
- Chen, S. et al. More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic β-cell signaling. Diabetes 43, 878–883 (1994).
CAS PubMed Google Scholar
- Mulder, H. et al. Overexpression of a modified human malonyl-CoA decarboxylase blocks the glucose-induced increase in malonyl-CoA level but has no impact on insulin secretion in INS-1-derived (832/13) β-cells. J. Biol. Chem. 276, 6479–6484 (2001).
CAS PubMed Google Scholar
- Roduit, R. et al. Glucose down-regulates the expression of the peroxisome proliferator-activated receptor-α gene in the pancreatic β-cell. J. Biol. Chem. 275, 35799–35806 (2000).
CAS PubMed Google Scholar
- Schuit, F. et al. Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in β-cells. J. Biol. Chem. 272, 18572–18579 (1997).
CAS PubMed Google Scholar
- da Silva Xavier, G. et al. Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression. Biochem. J. 371, 761–774 (2003).
CAS PubMed PubMed Central Google Scholar
- Salt, I. P., Johnson, G., Ashcroft, S. J. & Hardie, D. G. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic β-cells, and may regulate insulin release. Biochem. J. 335, 533–539 (1998).
CAS PubMed PubMed Central Google Scholar
- Brun, T., Roche, E., Kim, K. H. & Prentki, M. Glucose regulates acetyl-CoA carboxylase gene expression in a pancreatic β-cell line (INS-1). J. Biol. Chem. 268, 18905–18011 (1993).
CAS PubMed Google Scholar
- Roche, E. et al. Long-term exposure of β-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression. Diabetes 47, 1086–1094 (1998).
CAS PubMed Google Scholar
- Andreolas, C. et al. Stimulation of acetyl-CoA carboxylase gene expression by glucose requires insulin release and sterol regulatory element binding protein 1c in pancreatic MIN6 β-cells. Diabetes 51, 2536–2545 (2002).
CAS PubMed Google Scholar
- El-Assaad, W. et al. Saturated fatty acids synergize with elevated glucose to cause pancreatic β-cell death. Endocrinology 144, 4154–4163 (2003). Demonstration that elevated glucose and saturated fatty acids synergize in causing pancreatic β-cell death and that glucolipotoxicity is antagonized by AMPK activators.
CAS PubMed Google Scholar
- Ido, Y., Carling, D. & Ruderman, N. Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation. Diabetes 51, 159–167 (2002). Demonstration that hyperglycaemia-induced increases in malonyl-CoA, mitochondrial dysfunction and insulin resistance in the endothelial cell are prevented by AMPK activation.
CAS PubMed Google Scholar
- Knowler, W. C. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002).
CAS PubMed Google Scholar
- Buchanan, T. A. et al. Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes 51, 2796–2803 (2002).
CAS PubMed Google Scholar
- Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).
CAS PubMed Google Scholar
- Steinberg, H. O. & Baron, A. D. Vascular function, insulin resistance and fatty acids. Diabetologia 45, 623–634 (2002).
CAS PubMed Google Scholar
- Chen, Z. P. et al. AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett. 443, 285–289 (1999).
CAS PubMed Google Scholar
- Ido, Y. et al. The AMP-kinase (AMPK) activator, AICAR, inhibits the increase in oxidative stress induced by hyperglycemia and palmitate. Diabetes 51, A396 (2002).
Google Scholar
- Yu, A. S., Keeffe, E. B. Nonalcoholic fatty liver disease. Rev. Gastroenterol. Disord. 2, 11–19 (2002).
PubMed Google Scholar
- Neuschwander-Tetri, B. A. & Caldwell, S. H. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 37, 1202–1219 (2003).
PubMed Google Scholar
- Koteish, A. & Diehl, A. M. Animal models of steatosis. Semin. Liver Dis. 21, 89–104 (2001).
CAS PubMed Google Scholar
- Green, R. M. NASH—hepatic metabolism and not simply the metabolic syndrome. Hepatology 38, 14–17 (2003).
CAS PubMed Google Scholar
- Lam, T. K. et al. Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta. Am. J. Physiol. Endocrinol. Metab. 283, E682–E691 (2002).
CAS PubMed Google Scholar
- Brownlee, M. Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813–820 (2001).
CAS PubMed Google Scholar
- Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S. & Goldstein, J. L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401, 73–76 (1999).
CAS PubMed Google Scholar
- Xu, A., Wang, Y. et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver disease in mice. J. Clin. Invest. 112, 91–100 (2003).
CAS PubMed PubMed Central Google Scholar
- Neuschwander-Tetri, B. A. et al. Improved Nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. Hepatology 38, 1008–1017 (2003).
CAS PubMed Google Scholar
- Yamauchi, T. et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nature Med. 8, 1288–1295 (2002).
CAS PubMed Google Scholar
- Tomas, E. et al. 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 99, 16309–16313 (2002).
CAS PubMed PubMed Central Google Scholar
- Corton, J. M., Gillespie, J. G., Hawley, S. A. & Hardie, D. G. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells. Eur. J. Biochem. 229, 558–565 (1995).
CAS PubMed Google Scholar
- Park, H. et al. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J. Biol. Chem. 277, 32571–32577 (2002).
CAS PubMed Google Scholar
- Moule, S. K. & Denton, R. M. The activation of p38 MAPK by the β-adrenergic agonist isoproterenol in rat epididymal fat cells. FEBS Lett. 439, 287–290 (1998).
CAS PubMed Google Scholar
- Wu, X. et al. Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 52, 1355–1363 (2003).
CAS PubMed Google Scholar
- Ruderman, N., Saha, A. & Kraegen, E. W. Malonyl CoA, AMP–activated protein kinase, and adiposity. Endocrinology 144, 5161–5171 (2003).
Google Scholar
- Richter, E. A., Garetto, L. P., Goodman, M. N. & Ruderman, N. B. Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin. J. Clin. Invest. 69, 785–793 (1982).
CAS PubMed PubMed Central Google Scholar
- Skerrett, P. J. & Manson, J. E. in Handbook of Exercise in Diabetes 2nd edn (eds Ruderman, N., Devlin, J. R., Schneider, S. H. & Kriska, A.) 158–182 (American Diabetes Association, Alexandria, 2002).
Google Scholar
- Pan, X. R. et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20, 537–544 (1997).
CAS PubMed Google Scholar
- Tuomilehto, J. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 344, 1343–1350 (2001).
CAS PubMed Google Scholar
- Fruebis, J. et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc. Natl Acad. Sci. USA 98, 2005–2010 (2001).
CAS PubMed PubMed Central Google Scholar
- Rajala, M. W., Scherer, P. E. The adipocyte — at the crossroads of energy homeostasis, inflammation and atherosclerosis. Endocrinology 144, 3765–3773 (2003).
CAS PubMed Google Scholar
- Maeda, N. et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Med. 8, 731–737 (2002).
CAS PubMed Google Scholar
- Okamoto, Y. et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106, 2767–2770 (2002).
CAS PubMed Google Scholar
- Yamauchi, T. et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J. Biol. Chem. 278, 2461–2468 (2003).
CAS PubMed Google Scholar
- Matsuzawa, Y., Funahashi, T. & Nakamura, T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann. NY Acad. Sci. 892, 146–154 (1999).
CAS PubMed Google Scholar
- Ido, Y., Yagihashi, N., Cacicedo, J. M., Ruderman, N. B. AMP-kinase activation prevents TNF-α induced ICAM expression by inhibiting NF-κB transactivation but not by inhibiting their translocation or DNA-binding. Diabetes 51, A458 (2002).
Google Scholar
- Goldfine, A. B. & Kahn, C. R. Adiponectin: linking the fat cell to insulin sensitivity. Lancet 362, 1431–1432 (2003).
PubMed Google Scholar
- Minokoshi, Y. et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415, 339–343 (2002). First demonstration that an endogenous hormone leptin may act, at least in part, by activating AMPK.
CAS PubMed Google Scholar
- Olefsky, J. M. Treatment of insulin resistance with peroxisome proliferator-activated receptor-γ agonists. J. Clin. Invest. 106, 467–472 (2000).
CAS PubMed PubMed Central Google Scholar
- Mayerson, A. B. et al. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 51, 797–802 (2002).
CAS PubMed Google Scholar
- Hsueh, W. A. & Law, R. The central role of fat and effect of peroxisome proliferator-activated receptor-γ on progression of insulin resistance and cardiovascular disease. Am. J. Cardiol. 92, 3J–9J (2003).
CAS PubMed Google Scholar
- Haffner, S. M. Insulin resistance, inflammation, and the prediabetic state. Am. J. Cardiol. 92, 18J–26J (2003).
CAS PubMed Google Scholar
- Saha, A., Ye, J., Assiti, M., Kraegen, E., Ruderman, N. B. & Arilucca, P. R. Pioglitazone treatment activates AMP-activated protein kinase (AMPK) in both liver and adipose tissue in the rat. Biochem. Biophys. Res. Commun. 314, 580–585 (2004).
CAS PubMed Google Scholar
- Yu, J. G. et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51, 2968–2974 (2002).
CAS PubMed Google Scholar
- Tanaka, T. et al. Activation of peroxisome proliferator-activated receptor delta induces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc. Natl Acad. Sci. USA 100, 15924–15929 (2003).
CAS PubMed PubMed Central Google Scholar
- Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174 (2001). First report that the insulin-sensitizing anti-diabetic agent metformin activates AMPK.
CAS PubMed PubMed Central Google Scholar
- Musi, N. et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51, 2074–2081 (2002).
CAS PubMed Google Scholar
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352, 854–865 (1998).
- Evans, J. L., Goldfine, I. D., Maddux, B. A. & Grodsky, G. M. Are oxidative stress-activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes 52, 1–8 (2003).
CAS PubMed Google Scholar
- Inoguchi, T. et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49, 1939–1945 (2000).
CAS PubMed Google Scholar
- Summers, S. A., Garza, L. A., Zhou, H. & Birnbaum, M. J. Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Mol. Cell. Biol. 18, 5457–5464 (1998).
CAS PubMed PubMed Central Google Scholar
- Blazquez, C., Geelen, M. J., Velasco, G. & Guzman, M. The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. FEBS Lett. 489, 149–153 (2001).
CAS PubMed Google Scholar
- Cacicedo, J. M., Yagihashi, N., Adachi, T., Ruderman, N. R., and Yasudo, I. Palmitate-induced cultured bovine retinal pericyte (BRP) apoptosis is inhibited by activating AMP–activated protein kinase (AMPK), by expression of Cu, Zn superoxide dismutase (SOD1) and dominant negative mutant IκB. Diabetes 52, A199 (2003).
Google Scholar
- Yu, C. et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem. 277, 50230–50236 (2002).
CAS PubMed Google Scholar
- Marshall, S. The hexosamine signaling pathway: a new road to drug discovery. Curr. Opin. Endocrinol. Diabetes 9, 160–167 (2002).
CAS Google Scholar
- Veerababu, G. et al. Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance. Diabetes 49, 2070–2078 (2000).
CAS PubMed Google Scholar
- Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genet. 34, 267–273 (2003).
CAS PubMed Google Scholar
- Patti, M. E. et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc. Natl Acad. Sci. USA 100, 8466–8471 (2003).
CAS PubMed PubMed Central Google Scholar
- Kelley, D. E., He, J., Menshikova, E. V. & Ritov, V. B. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51, 2944–2950 (2002).
CAS PubMed Google Scholar
- Petersen, K. F. et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300, 1140–1142 (2003).
CAS PubMed PubMed Central Google Scholar
- Schneider, S. H., Khachadurian, A. K., Amorosa, L. F., Clemow, L. & Ruderman, N. B. Ten-year experience with an exercise-based outpatient life-style modification program in the treatment of diabetes mellitus. Diabetes Care 15, 1800–1810 (1992).
CAS PubMed Google Scholar
- Diehl, A. M. Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines. Am. J. Physiol. Gastrointest. Liver Physiol. 282, G1–G5 (2002).
CAS PubMed Google Scholar
- Maestre, I. et al. Mitochondrial dysfunction is involved in apoptosis induced by serum withdrawal and fatty acids in the β-cell line INS-1. Endocrinology 144, 335–345 (2003).
CAS PubMed Google Scholar
- Zong, H. et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in resonse to chronic energy deprivation. Proc. Natl Acad. Sci. USA 99, 15983–15987 (2002).
CAS PubMed PubMed Central Google Scholar
- Reitman, M. L. Metabolic lessons from genetically lean mice. Annu. Rev. Nutr. 22, 459–482 (2002).
CAS PubMed Google Scholar
- Gavrilova, O. et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J. Clin. Invest. 105, 271–278 (2000).
CAS PubMed PubMed Central Google Scholar
- Haque, W. A., Shimomura, I., Matsuzawa, Y. & Garg, A. serum adiponectin and leptin levels in patients with lipodystrophies. J. Clin. Endocrinol. Metab. 87, 2395 (2002).
CAS PubMed Google Scholar
- Arioglu, E. et al. Leptin replacement therapy for lipodystrophy. N. Engl. J. Med. 346, 570–578 (2002).
Google Scholar
- Petersen, K. F. et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J. Clin. Invest. 109, 1345–1350 (2002).
CAS PubMed PubMed Central Google Scholar
- Sbraccia, P. et al. Rosiglitazone treatment improves insulin sensitivity in lipodystrophic patients with mandibuloacral displasia. Diabetes 52, A1 (2003).
Google Scholar
- Yamauchi, T. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Med. 7, 941–946 (2001).
CAS PubMed Google Scholar
- Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. & Wakil, S. J. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291, 2613–2616 (2001). Demonstration that a lack of ACC2 enhances insulin sensitivity and leads to decreased adiposity despite an increase in food intake.
CAS PubMed Google Scholar
- Winder, W. W. & Hardie, D. G. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol. 277, E1–E10 (1999).
CAS PubMed Google Scholar
- Bavenholm, P. V., Pigon, J., Saha, A. K., Ruderman, N. B. & Efendic, S. Fatty acid oxidation and the regulation of malonyl-CoA in human muscle. Diabetes 49, 1078–1083 (2000).
CAS PubMed Google Scholar
- Dean, D. et al. Exercise diminishes the activity of acetyl-CoA carboxylase in human muscle. Diabetes 49, 1295–1300 (2000).
CAS PubMed Google Scholar
- Chien, D., Dean, D., Saha, A. K., Flatt, J. P. & Ruderman, N. B. Malonyl–CoA content and fatty acid oxidation in rat muscle and liver in vivo. Am. J. Physiol. Endocrinol. Metab. 279, E259–E265 (2000).
CAS PubMed Google Scholar
- Vavvas, D. et al. Contraction-induced changes in acetyl-CoA carboxylase and 5′-AMP-activated kinase in skeletal muscle. J. Biol. Chem. 272, 13255–13261 (1997).
CAS PubMed Google Scholar
- Winder, W. W. & Hardie, D. G. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am. J. Physiol. 270, E299–E304 (1996). Initial demonstration that exercise activates AMPK in skeletal muscle.
CAS PubMed Google Scholar
- Habinowski, S. A. et al. Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line. Arch. Biochem. Biophys. 396, 71–79 (2001).
CAS PubMed Google Scholar
- Hardie, D. G., Scott, J. W., Pan, D. A. & Hudson, E. R. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett. 546, 113–120 (2003). Recent review of developments in AMPK biochemistry and action.
CAS PubMed Google Scholar
- Hawley, S. A. et al. Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2, 28 (2003).
PubMed PubMed Central Google Scholar
- Ruderman, N. B. et al. AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise. Acta. Physiol. Scand. 178, 435–442 (2003).
CAS PubMed Google Scholar
- Robertson, R. P., Harmon, J., Tran, P. O., Tanaka, Y. & Takahashi, H. Glucose toxicity in β-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52, 581–587 (2003).
CAS PubMed Google Scholar
- Eto, K. Y. T., Matsui, J., Terauchi, Y., Noda, M. & Kadowaki, T. Genetic manipulations of fatty acid metabolism in β-cells are associated with dysregulated insulin secretion. Diabetes 51, S414–S420 (2002).
CAS PubMed Google Scholar
- Wang, H. et al. The transcription factor SREBP-1c is instrumental in the development of β-cell dysfunction. J. Biol. Chem. 278, 16622–16629 (2003).
CAS PubMed Google Scholar
- Lupi, R. et al. Lipotoxicity in human pancreatic islets and the protective effect of metformin. Diabetes 51, S134–S137 (2002).
CAS PubMed Google Scholar
- Sreenan, S., Sturis, J., Pugh, W., Burant, C. F. & Polonsky, K. S. Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone. Am. J. Physiol. 271, E742–E747 (1996).
CAS PubMed Google Scholar
- Roduit, R. et al. A role for the malonyl-CoA/long chain acyl-CoA pathway of lipid signalling in the regulation of insulin secretion in response to both fuel and non-fuel stimuli. Diabetes (in the press).