Mechanisms of the free fatty acid-induced increase in hepatic glucose production

American Journal of Physiology - Endocrinology and Metabolism

Volumn 284, Issue 5 47-5, 2003, Pages

  Lam, Tony K T ^a   Carpentier, André ^b   Lewis, Gary F ^a   Van de Werve, Gérald ^c   Fantus, I George ^a   Giacca, Adria ^a,d  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITÉ DE SHERBROOKE   (Canada)

^c UNIVERSITY OF MONTREAL   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

Author keywords

Hepatic insulin resistance; Lipid

Indexed keywords

FATTY ACID; INSULIN;

DISEASE ASSOCIATION; FATTY ACID BLOOD LEVEL; GLUCONEOGENESIS; GLUCOSE METABOLISM; HORMONE ACTION; HUMAN; HYPERINSULINEMIA; INSULIN RESISTANCE; LIVER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW;

EID: 0344406146     PISSN: 01931849     EISSN: None     Source Type: Journal    
DOI: 10.1152/ajpendo.00033.2003     Document Type: Review

References (134)

1. Adeli K, Taghibiglou C, Van Iderstine SC, and Lewis GF. Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistance. Trends Cardiovasc Med 11: 170-176, 2001.
2. Agius L and Peak M. Binding and translocation of glucokinase in hepatocytes. Biochem Soc Trans 25: 145-150, 1997.
3. Andrieu-Abadie N, Gouaze V, Salvayre R, and Levade T. Ceramide in apoptosis signaling: relationship with oxidative stress. Free Radic Biol Med 31: 717-728, 2001.
4. Antras-Ferry J, Le Bigot G, Robin P, Robin D, and Forest C. Stimulation of phosphoenolpyruvate carboxykinase gene expression by fatty acids. Biochem Biophys Res Commun 203: 385-391, 1994.
5. Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, and Vidal H. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 46: 1319-1327, 1997.
6. Baldeweg SE, Golay A, Natali A, Balkau B, Del Prato S, and Coppack SW. Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans. European Group for the Study of Insulin Resistance (EGIR). Eur J Clin Invest 30: 45-52, 2000.
7. Baron AD, Brechtel G, and Edelman SV. Effects of free fatty acids and ketone bodies on in vivo non-insulin-mediated glucose utilization and production in humans. Metabolism 38: 1056-1061, 1989.
8. Barzilai N, She L, Liu BQ, Vuguin P, Cohen P, Wang J, and Rossetti L. Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes 48: 94-98, 1999.
9. Bevilacqua S, Bonadonna R, Buzzigoli G, Boni C, Ciociaro D, Maccari F, Giorico MA, and Ferrannini E. Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects. Metabolism. 36: 502-506, 1987.
10. Blair AS, Hajduch E, Litherland GJ, and Hundal HS. Regulation of glucose transport and glycogen synthesis in L6 muscle cells during oxidative stress. Evidence for cross-talk between the insulin and SAPK2/p38 mitogen-activated protein kinase signaling pathways. J Biol Chem 274: 36293-36299, 1999.
11. Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46: 3-10, 1997.
12. Boden G, Chen X, Capulong E, and Mozzoli M. Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes. Diabetes 50: 810-816, 2001.
13. Boden G, Chen X, Ruiz J, White JV, and Rossetti L. Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93: 2438-2446, 1994.
14. Boden G and Jadali F. Effects of lipid on basal carbohydrate metabolism in normal men. Diabetes 40: 686-692, 1991.
15. Bolinder J, Kerckhoffs DA, Moberg E, Hagstrom-Toft E, and Arner P. Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects. Diabetes 49: 797-802, 2000.
16. Bollag GE, Roth RA, Beaudoin J, Mochly-Rosen D, and Koshland DE Jr. Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity. Proc Natl Acad Sci USA 83: 5822-5824, 1986.
17. Brindley DN, Wang CN, Mei J, Xu J, and Hanna AN. Tumor necrosis factor-alpha and ceramides in insulin resistance. Lipids 34, Suppl: S85-S88, 1999.
18. Carling D, Zammit VA, and Hardie DG. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 223: 217-222, 1987.
19. Chen MT, Kaufman LN, Spennetta T, and Shrago E. Effects of high fat-feeding to rats on the interrelationship of body weight, plasma insulin, and fatty acyl-coenzyme A esters in liver and skeletal muscle. Metabolism 41: 564-569, 1992.
20. Chen X, Iqbal N, and Boden G. The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects. J Clin Invest 103: 365-372, 1999.
21. Chin JE, Dickens M, Tavare JM, and Roth RA. Over expression of protein kinase C isoenzymes alpha, beta I, gamma, and epsilon in cells overexpressing the insulin receptor. Effects on receptor phosphorylation and signaling. J Biol Chem 268: 6338-6347, 1993.
22. Cho C, Elowe S, Newton B, Giacca A, and Fantus IG. NAC (N-acetylcysteine) prevents hyperglycemia and glucosamine-induced insulin resistance in vitro and in vivo by different mechanisms (Abstract). Diabetes 48, Suppl 1: A257, 1999.
23. Chu CA, Sherck SM, Igawa K, Sindelar DK, Neal DW, Emshwiller M, and Cherrington AD. Effects of free fatty acids on hepatic glycogenolysis and gluconeogenesis in conscious dogs. Am J Physiol Endocrinol Metab 282: E402-E411, 2002.
24. Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance. Br J Nutr 83, Suppl 1: S59-S66, 2000.
25. Clore JN, Glickman PS, Nestler JE, and Blackard WG. In vivo evidence for hepatic autoregulation during FFA-stimulated gluconeogenesis in normal humans. Am J Physiol Endocrinol Metab 261: E425-E429, 1991.
26. Combs TP, Berg AH, Obici S, Scherer PE, and Rossetti L. Endogenous glucose production is inhibited by the adiposederived protein Acrp30. J Clin Invest 108: 1875-1881, 2001.
27. Considine RV, Nyce MR, Allen LE, Morales LM, Triester S, Serrano J, Colberg J, Lanza-Jacoby S, and Caro JF. 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.
28. Cook SA, Matsui T, Li L, and Rosenzweig A. Transcriptional effects of chronic Akt activation in the heart. J Biol Chem 277: 22528-22533, 2002.
29. Coppack SW, Evans RD, Fisher RM, Frayn KN, Gibbons GF, Humphreys SM, Kirk ML, Potts JL, and Hockaday TD. Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal. Metabolism 41: 264-272, 1992.
30. De Fea K and Roth RA. Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612. Biochemistry 36: 12939-12947, 1997.
31. Diaz-Guerra MJ, Junco M, and Bosca L. Oleic acid promotes changes in the subcellular distribution of protein kinase C in isolated hepatocytes. J Biol Chem 266: 23568-23576, 1991.
32. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, and Brownlee M. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 97: 12222-12226, 2000.
33. Ercan-Fang N, Gannon MC, Rath VL, Treadway JL, Taylor MR, and Nuttall FQ. Integrated effects of multiple modulators on human liver glycogen phosphorylase α. Am J Physiol Endocrinol Metab 283: E29-E37, 2002.
34. Fantus IG, Haber A, Lam T, Gupta N, and Giacca A. N-acetyl-L-cysteine prevents insulin resistance due to glucotoxicity and lipotoxicity in vivo (Abstract). Diabetologia 43, Suppl 1: A152, 2000.
35. Ferrannini E, Barrett EJ, Bevilacqua S, and DeFronzo RA. Effect of fatty acids on glucose production and utilization in man. J Clin Invest 72: 1737-1747, 1983.
36. Fong DG, Nehra V, Lindor KD, and Buchman AL. Metabolic and nutritional considerations in nonalcoholic fatty liver. Hepatology 32: 3-10, 2000.
37. Gabbay RA, Sutherland C, Gnudi L, Kahn BB, O'Brien RM, Granner DK, and Flier JS. Insulin regulation of phosphoenolpyruvate carboxykinase gene expression does not require activation of the Ras/mitogen-activated protein kinase signaling pathway. J Biol Chem 271: 1890-1897, 1996.
38. Garcia-Ruiz C, Colell A, Mari M, Morales A, and Fernandez-Checa JC. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J Biol Chem 272: 11369-11377, 1997.
39. Giacca A, Fisher SJ, Shi ZQ, Gupta R, Lickley HL, and Vranic M. Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs. J Clin Invest 90: 1769-1777, 1992.
40. Golay A, Swislocki AL, Chen YD, and Reaven GM. Relationships between plasma-free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and non-insulin-dependent diabetic individuals. Metabolism 36: 692-696, 1987.
41. Goldberg HJ, Whiteside CI, and Fantus IG. The hexosamine pathway regulates the plasminogen activator inhibitor-1 gene promoter and Sp1 transcriptional activation through protein kinase C-beta I and -delta. J Biol Chem 277: 33833-33841, 2002.
42. Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, and Shulman GI. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 48: 1270-1274, 1999.
43. Hajduch E, Balendran A, Batty IH, Litherland GJ, Blair AS, Downes CP, and Hundal HS. Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss in downstream signalling in L6 skeletal muscle cells. Diabetologia 44: 173-183, 2001.
44. Hardie DG and Carling D. The AMP-activated protein kinase - fuel gauge of the mammalian cell? Eur J Biochem 246: 259-273, 1997.
45. Hawkins M, Barzilai N, Liu R, Hu M, Chen W, and Rossetti L. Role of the glucosamine pathway in fat-induced insulin resistance. J Clin Invest 99: 2173-2182, 1997.
46. Helenius A and Aebi M. Intracellular functions of N-linked glycans. Science 291: 2364-2369, 2001.
47. Hems DA and Whitton PD. Control of hepatic glycogenolysis. Physiol Rev 60: 1-50, 1980.
48. Henry RR. Impaired muscle fat metabolism: a cause or effect of visceral obesity? J Clin Invest 95: 1427-1428, 1995.
49. Herzog B, Waltner-Law M, Scott DK, Eschrich K, and Granner DK. Characterization of the human liver fructose-1,6-bisphosphatase gene promoter. Biochem J 351: 385-392, 2000.
50. Hickson-Bick DL, Buja ML, and McMillin JB. Palmitatemediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. J Mol Cell Cardiol 32: 511-519, 2000.
51. Iglesias MA, Ye JM, Frangioudakis G, Saha AK, Tomas E, Ruderman NB, Cooney GJ, and Kraegen EW. AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 51: 2886-2894, 2002.
52. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, and Nawata H. 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.
53. Itani SI, Ruderman NB, Schmieder F, and Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51: 2005-2011, 2002.
54. Itani SI, Zhou Q, Pories WJ, MacDonald KG, and Dohm GL. Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity. Diabetes 49: 1353-1358, 2000.
55. Kellerer M, Mushack J, Seffer E, Mischak H, Ullrich A, and Haring HU. Protein kinase C isoforms alpha, delta and theta require insulin receptor substrate-1 to inhibit the tyrosine kinase activity of the insulin receptor in human kidney embryonic cells (HEK 293 cells). Diabetologia 41: 833-838, 1998.
56. Kelley DE and Mandarino LJ. Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677-683, 2000.
57. Kemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, and Witters LA. Dealing with energy demand: the AMP-activated protein kinase. Trends Biochem Sci 24: 22-25, 1999.
58. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, and Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 103: 1489-1498, 1999.
59. Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, and Shulman GI. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci USA 98: 7522-7527, 2001.
60. Kim JK, Gavrilova O, Chen Y, Reitman ML, and Shulman GI. Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem 275: 8456-8460, 2000.
61. Kim JK, Kim YJ, Fillmore JJ, Chen Y, Moore I, Lee J, Yuan M, Li ZW, Karin M, Perret P, Shoelson SE, and Shulman GI. Prevention of fat-induced insulin resistance by salicylate. J Clin Invest 108: 437-446, 2001.
62. Kolm-Litty V, Tippmer S, Haring HU, and Schleicher E. Glucosamine induces translocation of protein kinase C isoenzymes in mesangial cells. Exp Clin Endocrinol Diabetes 106: 377-383, 1998.
63. Kowluru RA, Kern TS, and Engerman RL. Abnormalities of retinal metabolism in diabetes or experimental galactosemia. IV. Antioxidant defense system. Free Radic Biol Med 22: 587-592, 1997.
64. Kubota N, Tobe K, Terauchi Y, Eto K, Yamauchi T, Suzuki R, Tsubamoto Y, Komeda K, Nakano R, Miki H, Satoh S, Sekihara H, Sciacchitano S, Lesniak M, Aizawa S, Nagai R, Kimura S, Akanuma Y, Taylor SI, and Kadowaki T. Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia. Diabetes 49: 1880-1889, 2000.
65. Kusunoki M, Tsutsumi K, Hara T, Ogawa H, Nakamura T, Miyata T, Sakakibara F, Fukuzawa Y, Suga T, Kakumu S, and Nakaya Y. Correlation between lipid and glycogen contents in liver and insulin resistance in high-fat-fed rats treated with the lipoprotein lipase activator NO-1886. Metabolism 51: 792-795, 2002.
66. Lam TK, Nassan A, Kim T, Uchino H, and Giacca A. Short-term elevation of polyunsaturated fatty acids induce less hepatic insulin resistance than saturated or monounsaturated fatty acids (Abstract). Diabetes 51, Suppl 2: A42, 2002.
67. Lam TK, van de Werve G, and Giacca A. Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites. Am J Physiol Endocrinol Metab 284: E281-E290, 2003.
68. Lam TK, Yoshii H, Haber CA, Bogdanovic E, Lam L, Fantus IG, and Giacca A. Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-δ. Am J Physiol Endocrinol Metab 283: E682-E691, 2002.
69. Latasa MJ, Moon YS, Kim KH, and Sul HS. Nutritional regulation of the fatty acid synthase promoter in vivo: sterol regulatory element binding protein functions through an upstream region containing a sterol regulatory element. Proc Natl Acad Sci USA 97: 10619-10624, 2000.
70. Laws A, Hoen HM, Selby JV, Saad MF, Haffner SM, and Howard BV. Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Arterioscler Thromb Vasc Biol 17: 64-71, 1997.
71. Leclerc I, Lenzner C, Gourdon L, Vaulont S, Kahn A, and Viollet B. Hepatocyte nuclear factor-4alpha involved in type 1 maturity-onset diabetes of the young is a novel target of AMP-activated protein kinase. Diabetes 50: 1515-1521, 2001.
72. Lee KU, Park JY, Kim CH, Hong SK, Suh KI, Park KS, and Park SW. Effect of decreasing plasma free fatty acids by acipimox on hepatic glucose metabolism in normal rats. Metabolism 45: 1408-1414, 1996.
73. Lewis GF, Carpentier A, Adeli K, and Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23: 201-229, 2002.
74. Lewis GF, Vranic M, Harley P, and Giacca A. Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans. Diabetes 46: 1111-1119, 1997.
75. Leyton J, Drury PJ, and Crawford MA. Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. Br J Nutr 57: 383-393, 1987.
76. Liu YQ and Uyeda K. A mechanism for fatty acid inhibition of glucose utilization in liver. Role of xylulose 5-P. J Biol Chem 271:8824-8830, 1996.
77. Magnusson I, Rothman DL, Katz LD, Shulman RG, and Shulman GI. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest 90: 1323-1327, 1992.
78. Massillon D, Barzilai N, Hawkins M, Prus-Wertheimer D, and Rossetti L. Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes 46: 153-157, 1997.
79. Mathias S, Pena LA, and Kolesnick RN. Signal transduction of stress via ceramide. Biochem J 335: 465-480, 1998.
80. Maziere C, Dantin F, Conte MA, Degonville J, Ali D, Dubois F, and Maziere JC. Polyunsaturated fatty acid enrichment enhances endothelial cell-induced low-density-lipoprotein peroxidation. Biochem J 336: 57-62, 1998.
81. McCune SA, Durant PJ, Jenkins PA, and Harris RA. Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats. Metabolism 30: 1170-1178, 1981.
82. McGarry JD. Glucose-fatty acid interactions in health and disease. Am J Clin Nutr 67: 500S-504S, 1998.
83. McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51: 7-18, 2002.
84. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, and Kahn CR. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6: 87-97, 2000.
85. Miyazaki Y, Glass L, Triplitt C, Wajeberg E, Mandarino LJ, and DeFronzo RA. Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 283: E1135-E1143, 2002.
86. Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, Feigenbaum L, Lee E, Aoyama T, Eckhaus M, Reitman ML, and Vinson C. Life without white fat: a transgenic mouse. Genes Dev 12: 3168-3181, 1998.
87. Morand C, Besson C, Demigne C, and Remesy C. Importance of the modulation of glycolysis in the control of lactate metabolism by fatty acids in isolated hepatocytes from fed rats. Arch Biochem Biophys 309: 254-260, 1994.
88. Nakae J, Kitamura T, Silver DL, and Accili D. The forkhead transcription factor Foxol (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108: 1359-1367, 2001.
89. Nakae J, Park BC, and Accili D. Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a wortmannin-sensitive pathway. J Biol Chem 274:15982-15985, 1999.
90. Neschen S, Moore I, Regittnig W, Yu CL, Wang Y, Pypaert M, Petersen KF, and Shulman GI. Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab 282: E395-E401, 2002.
91. Oakes ND, Cooney GJ, Camilleri S, Chisholm DJ, and Kraegen EW. Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes 46: 1768-1774, 1997.
92. Olsen GS and Hansen BF. AMP kinase activation ameliorates insulin resistance induced by free fatty acids in rat skeletal muscle. Am J Physiol Endocrinol Metab 283: E965-E970, 2002.
93. Paolisso G, Gambardella A, Tagliamonte MR, Saccomanno F, Salvatore T, Gualdiero P, D'Onofrio MV, and Howard BV. Does free fatty acid infusion impair insulin action also through an increase in oxidative stress? J Clin Endocrinol Metab 81: 4244-4248, 1996.
94. Perreault M and Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 7: 1138-1143, 2001.
95. Qu X, Seale JP, and Donnelly R. Tissue and isoform-selective activation of protein kinase C in insulin-resistant obese Zucker rats - effects of feeding. J Endocrinol 162: 207-214, 1999.
96. Ravichandran LV, Esposito DL, Chen J, and Quon MJ. Protein kinase C-zeta phosphorylates insulin receptor substrate-1 and impairs its ability to activate phosphatidylinositol 3-kinase in response to insulin. J Biol Chem 276: 3543-3549, 2001.
97. Rebrin K, Steil GM, Mittelman SD, and Bergman RN. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest 98: 741-749, 1996.
98. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, and Shulman GI. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97: 2859-2865, 1996.
99. Roden M, Stingl H, Chandramouli V, Schumann WC, Hofer A, Landau BR, Nowotny P, Waldhausl W, and Shulman GI. Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans. Diabetes 49: 701-707, 2000.
100. Rother KI, Imai Y, Caruso M, Beguinot F, Formisano P, and Accili D. Evidence that IRS-2 phosphorylation is required for insulin action in hepatocytes. J Biol Chem 273: 17491-17497, 1998.
101. Ruderman NB, Saha AK, Vavvas D, and Witters LA. Malonyl-CoA, fuel sensing, and insulin resistance. Am J Physiol Endocrinol Metab 276: E1-E18, 1999.
102. Saloranta C, Koivisto V, Widen E, Falholt K, DeFronzo RA, Harkonen M, and Groop L. Contribution of muscle and liver to glucose-fatty acid cycle in humans. Am J Physiol Endocrinol Metab 264: E599-E605, 1993.
103. Saltiel AR. New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104: 517-529, 2001.
104. Saltiel AR and Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414: 799-806, 2001.
105. Samols E and Stagner JI. Intra-islet regulation. Am J Med 85: 31-35, 1988.
106. Samuel VT, Yu C, Chen Y, Zong H, and Shulman GI. Mechanism of fat induced hepatic insulin resistance (Abstract). Diabetes 51, Suppl 2: A68, 2002.
107. Schmitz-Peiffer C, Browne CL, Oakes ND, Watkinson A, Chisholm DJ, Kraegen EW, and Biden TJ. Alterations in the expression and cellular localization of protein kinase C isozymes epsilon and theta are associated with insulin resistance in skeletal muscle of the high-fat-fed rat. Diabetes 46: 169-178, 1997.
108. Schmitz-Peiffer C, Craig DL, and Biden TJ. Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem 274: 24202-24210, 1999.
109. Seifert R, Schachtele C, Rosenthal W, and Schultz G. Activation of protein kinase C by cis- and trans-fatty acids and its potentiation by diacylglycerol. Biochem Biophys Res Commun 154: 20-26, 1988.
110. Sindelar DK, Balcom JH, Chu CA, Neal DW, and Cherrington AD. A comparison of the effects of selective increases in peripheral or portal insulin on hepatic glucose production in the conscious dog. Diabetes 45: 1594-1604, 1996.
111. Sindelar DK, Chu CA, Rohlie M, Neal DW, Swift LL, and Cherrington AD. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes 46: 187-196, 1997.
112. Song S. Can the glyoxylate pathway contribute to fat-induced hepatic insulin resistance? Med Hypotheses 54: 739-747, 2000.
113. Song S, Andrikopoulos S, Filippis C, Thorburn AW, Khan D, and Proietto J. Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin. Am J Physiol Endocrinol Metab 281: E275-E282, 2001.
114. Sun X, Wu F, Datta R, Kharbanda S, and Kufe D. Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress. J Biol Chem 275:7470-7473, 2000.
115. Sun Z, Arendt CW, Ellmeier W, Schaeffer EM, Sunshine MJ, Gandhi L, Annes J, Petrzilka D, Kupfer A, Schwartzberg PL, and Littman DR. PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature 404: 402-407, 2000.
116. Taha C and Klip A. The insulin signaling pathway. J Membr Biol 169: 1-12, 1999.
117. Takayama S, White MF, and Kahn CR. Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity. J Biol Chem 263: 3440-3447, 1988.
118. Tirosh A, Potashnik R, Bashan N, and Rudich A. Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation. J Biol Chem 274: 10595-10602, 1999.
119. Tirosh A, Rudich A, Potashnik R, and Bashan N. Oxidative stress impairs insulin but not platelet-derived growth factor signalling in 3T3-L1 adipocytes. Biochem J 355: 757-763, 2001.
120. Tomsits E, Rischak K, and Szollar L. Long-term effects of unsaturated fatty acid dominance on the release of free radicals in the rat. Pediatr Res 36: 278-282, 1994.
121. Turinsky J, Bayly BP, and O'Sullivan DM. 1,2-Diacylglycerol and ceramide levels in rat liver and skeletal muscle in vivo. Am J Physiol Endocrinol Metab 261: E620-E627, 1991.
122. Van de Werve G. Non-Hormonal Regulation of Glycogenolysis. Short-Term Regulation of Liver Metabolism, edited by Hue L and van de Werve G. Amsterdam, The Netherlands: Elsevier North-Holland, 1981, p. 93-102.
123. Van de Werve G, Zaninetti D, Lang U, Vallotton MB, and Jeanrenaud B. Identification of a major defect in insulin resistant tissues of genetically obese (fa/fa) rats. Impaired protein kinase C. Diabetes 36: 310-314, 1987.
124. Wells L, Vosseller K, and Hart GW. Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc. Science 291: 2376-2378, 2001.
125. Wiesenthal SR, Sandhu H, McCall RH, Tchipashvili V, Yoshii H, Polonsky K, Shi ZQ, Lewis GF, Mari A, and Giacca A. Free fatty acids impair hepatic insulin extraction in vivo. Diabetes 48: 766-774, 1999.
126. Williamson JR, Browning ET, and Scholz R. Control mechanisms of gluconeogenesis and ketogenesis. I. Effects of oleate on gluconeogenesis in perfused rat liver. J Biol Chem 244: 4607-4616, 1969.
127. Williamson JR, Kreisberg RA, and Felts PW. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci USA 56: 247-254, 1966.
128. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, and White MF. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391: 900-904, 1998.
129. Xu J, Nakamura MT, Cho HP, and Clarke SD. Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats. J Biol Chem 274: 23577-23583, 1999.
130. 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, and Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8: 1288-1295, 2002.
131. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, and Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7: 941-946, 2001.
132. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, and Spiegelman BM. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413: 131-138, 2001.
133. Youn JH and Bergman RN. Enhancement of hepatic glycogen by gluconeogenic precursors: substrate flux or metabolic control? Am J Physiol Endocrinol Metab 258: E899-E906, 1990.
134. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, and Shoelson SE. Reversal of obesity- and dietinduced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293: 1673-1677, 2001.