Dysfunctional fat cells, lipotoxicity and type 2 diabetes

Ralph A. DeFronzo1
1Diabetes Division, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA. [email protected]

Tóm tắt

Từ khóa


Tài liệu tham khảo

DeFronzo, 1988, Lilly Lecture 1987. The triumvirate: cell, muscle, liver. A collusion responsible for NIDDM, Diabetes, 37, 667, 10.2337/diab.37.6.667

DeFronzo, 1997, Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes, Diabetes Rev, 3, 177

Kelley, 1995, Effects of weight loss on glucose homeostasis in NIDDM, Diabetes Rev, 3, 366

Schneider, 1995, Effects of fitness and physical training on carbohydrate metabolism and associated cardiovascular risk factors in patients with diabetes, Diabetes Rev, 3, 378

DeFronzo, 1985, Effects of insulin on peripheral and splanchnic glucose metabolism in non-insulindependent (type II) diabetes mellitus, J Clin Invest, 76, 149, 10.1172/JCI111938

Groop, 1989, Effect of insulin on oxidative and non-oxidative pathways of glucose and FFA metabolism in NIDDM. Evidence for multiple sites of insulin resistance, J Clin Invest, 84, 205, 10.1172/JCI114142

Shulman, 1990, Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin dependent diabetes by 13C nuclear magnetic resonance spectroscopy, N Engl J Med, 322, 223, 10.1056/NEJM199001253220403

DeFronzo, 1989, Fasting hyperglycemia in non-insulin dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake, Metabolism, 38, 387, 10.1016/0026-0495(89)90129-7

Gulli, 1992, The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents, Diabetes, 41, 1575, 10.2337/diab.41.12.1575

Tripathy, 2000, Insulin secretion and insulin sensitivity in relation to glucose tolerance. Lessons from the Botnia Study, Diabetes, 49, 975, 10.2337/diabetes.49.6.975

Pratipanawatr, 2001, Skeletal muscle insulin resistance in normoglycemic subjects with a strong family history of type 2 diabetes is associated with decreased insulin-stimulated insulin receptor substrate-1 tyrosine phosphorylation, Diabetes, 50, 2572, 10.2337/diabetes.50.11.2572

Jackson, 2000, Decreased insulin responsiveness of glucose uptake in cultured human skeletal muscle cells from insulin-resistant nondiabetic relatives of type 2 diabetic families, Diabetes, 49, 1169, 10.2337/diabetes.49.7.1169

Yalow, 1960, Immunoassay of endogenous plasma insulin in man, J Clin Invest, 39, 1157, 10.1172/JCI104130

Diamond, 1993, Glucose metabolism during the menstrual cycle: assessment by the euglycemic, hyperinsulinemic clamp technique, J Reprod Med, 38, 417

Reaven, 1989, Relationship between glucose tolerance, insulin secretion, and insulin action in non-obese individuals with varying degrees of glucose tolerance, Diabetologia, 32, 52, 10.1007/BF00265404

Vauhkonen, 1997, Defects in insulin secretion and insulin action in non-insulin-dependent diabetes mellitus are inherited. Metabolic studies on offspring of diabetic probands, J Clin Invest, 100, 86

Weyer, 1999, Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance, Diabetes, 48, 2197, 10.2337/diabetes.48.11.2197

Mitrakou, 1992, Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance, N Engl J Med, 326, 22, 10.1056/NEJM199201023260104

Polonsky, 1996, Non-insulin-dependent diabetes mellitus: a genetically programmed failure of the cell to compensate for insulin resistance, N Engl J Med, 334, 777, 10.1056/NEJM199603213341207

Kahn, 2001, The importance of cell failure in the development and progression of type 2 diabetes, J Clin Endocrinol Metab, 86, 4047

Jensen, 2002, Cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S, Diabetes, 51, 2170, 10.2337/diabetes.51.7.2170

Bogardus, 1984, Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects, J Clin Invest, 74, 1238, 10.1172/JCI111533

Saad, 1989, Sequential changes in serum insulin concentration during development of non-insulin-dependent diabetes, Lancet, 1, 1356, 10.1016/S0140-6736(89)92804-3

Ferrannini, 1988, The disposal of an oral glucose load in patients with non-insulin dependent diabetes, Metabolism, 37, 79, 10.1016/0026-0495(88)90033-9

Harris, 1998, Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U. S. adults. The Third National Health and Nutrition Examination Survey 1988-94, Diabetes Care, 21, 518, 10.2337/diacare.21.4.518

Pi-Sunyer, 1996, Weight and non-insulin-dependent diabetes mellitus, Am J Clin Nutr, 63, 426S, 10.1093/ajcn/63.3.426

Knowler, 1981, Diabetes incidence in Pima Indians: contributions of obesity and parental diabetes, Am J Epidemiol, 113, 144, 10.1093/oxfordjournals.aje.a113079

Carey, 1997, Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women: the Nurses' Health Study, Am J Epidemiol, 45, 614, 10.1093/oxfordjournals.aje.a009158

Mokdad, 2000, Diabetes trends in the United States 1990-98, Diabetes Care, 23, 1278, 10.2337/diacare.23.9.1278

Perry, 1999, Serum true insulin concentration and the risk of clinical non-insulin dependent diabetes during long-term follow-up, Int J Epidemiol, 28, 735, 10.1093/ije/28.4.735

Burke, 2001, Elevated incidence of type 2 diabetes in San Antonio, Texas, compared with that of Mexico City, Mexico, Diabetes Care, 24, 1573, 10.2337/diacare.24.9.1573

DeFronzo, 1978, Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding, J Clin Invest, 62, 204, 10.1172/JCI109108

Kolterman, 1980, Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects, J Clin Invest, 65, 1272, 10.1172/JCI109790

Ferrannini, 1997, Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR), J Clin Invest, 100, 1166, 10.1172/JCI119628

Bjorntorp, 1991, Metabolic implications of body fat distribution, Diabetes Care, 14, 1132, 10.2337/diacare.14.12.1132

Chan, 1994, Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men, Diabetes Care, 17, 961, 10.2337/diacare.17.9.961

Clausen, 1996, Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors, J Clin Invest, 98, 1195, 10.1172/JCI118903

Kissebah, 1989, Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus, Diabetes Metab Rev, 5, 83, 10.1002/dmr.5610050202

Despres, 1995, The insulin resistance-dyslipidemic syndrome: contribution of visceral obesity and therapeutic implications, Int J Obes Related Metab Disord, 19, S76

Banerji, 1995, Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive?, Diabetes, 44, 141, 10.2337/diab.44.2.141

Bonora, 1992, Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women, Diabetes, 41, 1151, 10.2337/diab.41.9.1151

Albu, 2000, Fat distribution and health in obesity, Ann N Y Acad Sci, 904, 491, 10.1111/j.1749-6632.2000.tb06505.x

Arner, 1997, Regional adipocity in man, J Endocrinol, 155, 191, 10.1677/joe.0.1550191

Zierath, 1998, Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signaling through the insulin receptor substrate-1-pathway, Diabetologia, 41, 1343, 10.1007/s001250051075

Reaven, 1988, Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 hours in patients with NIDDM, Diabetes, 37, 1020, 10.2337/diab.37.8.1020

Boden, 2002, Free fatty acids in obesity and type 2 diabetes. defining their role in the development of insulin resistance and cell dysfunction, Eur J Clin Invest, 32, 14, 10.1046/j.1365-2362.32.s3.3.x

Reaven, 1995, The fourth musketeer-from Alexandre Dumas to Claude Bernard, Diabetologia, 38, 3, 10.1007/BF02369347

Golay, 1988, Metabolic basis of obesity and noninsulin-dependent diabetes mellitus, Diabetes Metab Rev, 4, 727, 10.1002/dmr.5610040803

Boden, 1997, Role of fatty acids in the pathogenesis of insulin resistance and NIDDM, Diabetes, 46, 3, 10.2337/diab.46.1.3

McGarry, 2002, Banting Lecture 2001. dysregulation of fatty acid metabolism in the etiology of type 2 diabetes, Diabetes, 51, 7, 10.2337/diabetes.51.1.7

Kashyap, 2002, Chronic elevation in plasma free fatty acids impairs insulin secretion in non-diabetic offspring with a strong family history of T2DM, Diabetes, 51, A12

Goodpaster, 2000, Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus, Am J Clin Nutr, 71, 885, 10.1093/ajcn/71.4.885

Greco, 2002, Insulin resistance in morbid obesity. Reversal with intramyocellular fat depletion, Diabetes, 51, 144, 10.2337/diabetes.51.1.144

Seppala-Lindroos, 2002, 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, 10.1210/jcem.87.7.8638

Miyazaki, 2002, Effect of pioglitazone on liver fat content, abdominal fat distribution, and insulin sensitivity in patients with type 2 diabetes mellitus, Diabetes, 51, A69

Prentki, 1996, Are the B-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?, Diabetes, 45, 273, 10.2337/diab.45.3.273

Unger, 1996, Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. genetic and clinical implications, Diabetes, 45, 273

Shimabukuro, 1998, Fatty acid induced cell apoptosis, Proc Natl Acad Sci USA, 95, 2498, 10.1073/pnas.95.5.2498

Randle, 1963, The glucose fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus, Lancet, 1, 785, 10.1016/S0140-6736(63)91500-9

Felber, 1981, Glucose storage and oxidation in different degrees of human obesity measured by continuous indirect calorimetry, Diabetologia, 20, 39, 10.1007/BF00253814

Golay, 1984, Study on lipid metabolism in obesity diabetes, Metabolism, 33, 111, 10.1016/0026-0495(84)90121-5

Thiebaud, 1982, Effect of long chain triglyceride infusion on glucose metabolism in man, Metabolism, 21, 1128, 10.1016/0026-0495(82)90163-9

Roden, 1999, Rapid impairment of skeletal muscle glucose transport / phosphorylation by free fatty acids in humans, Diabetes, 48, 358, 10.2337/diabetes.48.2.358

Kelley, 2000, Fuel selection in human skeletal muscle in insulin resistance, Diabetes, 49, 677, 10.2337/diabetes.49.5.677

De Fea, 1997, Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612, Biochemistry, 36, 12939, 10.1021/bi971157f

Ravichandran, 2001, PKC-phosphorylates IRS-1 and impairs its ability to activate P-3-kinase in response to insulin, J Biol Chem, 276, 3543, 10.1074/jbc.M007231200

Faergeman, 1997, Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signaling, Biochem J, 323, 1, 10.1042/bj3230001

Kruszynska, 2002, Fatty acid-induced insulin resistance: decreased muscle PI3K activation but unchanged Akt phosphorylation, J Clin Endocrinol Metab, 87, 226, 10.1210/jcem.87.1.8187

Dresner, 1999, Effects of free fatty acids on glucose transport and IRS-1 associated phosphatidylinositol 3-kinase activity, J Clin Invest, 103, 253, 10.1172/JCI5001

Kashyap, 2002, A chronic physiologic increase in FFA in healthy subjects causes insulin signaling defects similar to those of insulin-resistant nondiabetic subjects with a strong family history of T2DM, Diabetes, 51, A24

Thompson, 2000, Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance, Diabetes, 49, 1761, 10.2337/diabetes.49.11.1761

Tippett, 1982, Anallosteric model for the inhibition of glucokinase by long chain acyl coenzyme A, J Biol Chem, 257, 14846

Wititsuwannakul, 1977, Mechanism of palmityl coenzyme A inhibition of liver glycogen synthase, J Biol Chem, 252, 7812, 10.1016/S0021-9258(17)41039-8

Schmitz-Peiffer, 1999, 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, 10.1074/jbc.274.34.24202

Chavez, 2003, A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids, J Biol Chem, 278, 10297, 10.1074/jbc.M212307200

DeFronzo, 1978, Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange, Proc Natl Acad Sci USA, 75, 5173, 10.1073/pnas.75.10.5173

DeFronzo, 1983, Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia, Diabetes, 32, 35, 10.2337/diab.32.1.35

Cherrington, 1999, Banting Lecture. Control of glucose uptake and release by the liver in vivo, Diabetes, 48, 1198, 10.2337/diabetes.48.5.1198

Mittelman, 2000, Inhibition of lipolysis causes suppression of endogenous glucose production independent of changes in insulin, Am J Physiol, 279, E630

Bevilacqua, 1987, Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects, Metabolism, 36, 502, 10.1016/0026-0495(87)90051-5

Golay, 1987, Relationships between plasma free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and non-insulin-dependent diabetic individuals, Metabolism, 36, 692, 10.1016/0026-0495(87)90156-9

Exton, 1969, Control of gluconeogenesis in liver. IV. Differential effects of fatty acids and glucagon on ketogenesis and gluconeogenesis in the perfused rat liver, J Biol Chem, 244, 4095, 10.1016/S0021-9258(17)36389-5

Bahl, 1997, In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase, Biochem Pharmacol, 53, 67, 10.1016/S0006-2952(96)00660-0

Williamson, 1966, Mechanisms for the stimulation of gluconeogenesis by fatty acids in perfused rat liver, Proc Natl Acad Sci USA, 56, 247, 10.1073/pnas.56.1.247

Massillon, 1997, Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion, Diabetes, 46, 153, 10.2337/diab.46.1.153

Lam, 2003, Mechanisms of the free fatty acid-induced increase in hepatic glucose production, Am J Physiol, 284, E863

Kim, 2001, Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance, Proc Natl Acad Sci USA, 98, 7522, 10.1073/pnas.121164498

Baron, 1987, Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics, Diabetes, 36, 274, 10.2337/diab.36.3.274

Matsuda, 2002, Dose-response curve relating plasma glucagon to hepatic glucose production and glucose disposal in type 2 diabetes mellitus, Metabolism, 51, 1111, 10.1053/meta.2002.34700

Waldhausl, 1982, Insulin production rate, hepatic insulin retention, and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinemic type II (non-insulin dependent) diabetes mellitus, Diabetologia, 23, 6, 10.1007/BF00257722

McGarry, 1999, Fatty acids, lipotoxicity and insulin secretion, Diabetologia, 42, 128, 10.1007/s001250051130

Warnotte, 1994, Mechanisms of the stimulation of insulin release by saturated fatty acids: a study of palmitate effects of mouse B-cells, Diabetes, 43, 703, 10.2337/diab.43.5.703

Stein, 1996, Essentially of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat, J Clin Invest, 97, 2728, 10.1172/JCI118727

Matschinsky, 1996, Banting Lecture 1995: a lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm, Diabetes, 45, 223, 10.2337/diab.45.2.223

Newgard, 1995, Metabolic coupling factors in pancreatic cell signal transduction, Annu Rev Biochem, 64, 689, 10.1146/annurev.bi.64.070195.003353

Zhou, 1994, Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle, J Clin Invest, 93, 870, 10.1172/JCI117042

Sako, 1990, A 48-h lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and cell oxidation through a process likely coupled to fatty acid oxidation, Endocrinology, 127, 1580, 10.1210/endo-127-4-1580

Mason, 1999, Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory response to glucose in vivo in rats, Diabetes, 48, 524, 10.2337/diabetes.48.3.524

Zhou, 1995, Long term exposure to fatty acids and ketones inhibits b-cell function in human pancreatic islets of Langerhans, J Clin Endocrinol Metab, 80, 1584

Unger, 1997, How obesity causes diabetes in Zucker diabetic fatty rats, Trends Endocrinol Metab, 7, 276, 10.1016/S1043-2760(97)00094-5

Lupi, 2002, Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets. Evidence that cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated, Diabetes, 51, 1437, 10.2337/diabetes.51.5.1437

Carpentier, 1999, Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation, Am J Physiol, 276, E1055

Paolisso, 1995, Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects, Diabetologia, 38, 1295, 10.1007/BF00401761

Carpentier, 2000, Prolonged elevation of plasma free fatty acids impair pancreatic B-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes, Diabetes, 49, 399, 10.2337/diabetes.49.3.399

Stefan, 2001, Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferators- activated receptor-2 gene, Diabetes, 50, 1143, 10.2337/diabetes.50.5.1143

Szczepaniak, 1999, GaMeasurement of intracellular triglyceride stores by H spectroscopy: validation in vivo, Am J Physiol, 276, E977

Perseghin, 1999, Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents, Diabetes, 48, 1600, 10.2337/diabetes.48.8.1600

Krssak, 1999, Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study, Diabetologia, 42, 113, 10.1007/s001250051123

Stein, 1999, Increasing intramyocellular triglyceride stores are associated with impaired glucose tolerance and NIDDM, Diabetes, 48, A287

Pan, 1997, Skeletal muscle triglyceride levels are inversely related to insulin action, Diabetes, 46, 983, 10.2337/diab.46.6.983

Sewter, 2002, Regional differences in the response of human pre-adipocytes to PPARγ and RXRα agonists, Diabetes, 51, 718, 10.2337/diabetes.51.3.718

Goodpaster, 1999, Effects of weight loss on regional fat distribution and insulin sensitivity in obesity, Diabetes, 48, 839, 10.2337/diabetes.48.4.839

Kelley, 1999, Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss, Am J Physiol, 277, E1130

Greco, 2002, Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion, Diabetes, 51, 144, 10.2337/diabetes.51.1.144

Bajaj, 2003, Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes mellitus, Diabetes, 52, 1364, 10.2337/diabetes.52.6.1364

Bajaj, 2004, Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients, J Clin Endocrinol Metab, 89, 200, 10.1210/jc.2003-031315

Ryysy, 2000, 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, 10.2337/diabetes.49.5.749

Pickup, 1998, Is type II diabetes mellitus a disease of the innate immune system?, Diabetologia, 41, 1241, 10.1007/s001250051058

Festa, 2000, Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS), Circulation, 102, 42, 10.1161/01.CIR.102.1.42

Fruhbeck, 2001, The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation, Am J Physiol, 280, E827

Bjorntorp, 1990, ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes, Arteriosclerosis, 10, 493, 10.1161/01.ATV.10.4.493

Arner, 2001, Regional differences in protein production by human adipose tissue, Biochem Soc Trans, 29, 72, 10.1042/bst0290072

Motoshima, 2002, Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes. effects of insulin and rosiglitazone, J Clin Endocrinol Metab, 87, 5662, 10.1210/jc.2002-020635

Berg, 2001, The adipocytesecreted protein Acrp30 enhances hepatic insulin action, Nat Med, 7, 947, 10.1038/90992

Combs, 2001, Endogenous glucose production is inhibited by the adipose-derived protein Acrp30, J Clin Invest, 108, 1875, 10.1172/JCI14120

Yamauchi, 2001, The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity, Nat Med, 7, 941, 10.1038/90984

Weyer, 2001, Hypoadiponectinemia in obesity and type 2 diabetes. close association with insulin resistance and hyperinsulinemia, J Clin Endocrinol Metab, 86, 1930, 10.1210/jcem.86.5.7463

Hotta, 2001, Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys, Diabetes, 50, 1126, 10.2337/diabetes.50.5.1126

Arita, 1999, Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity, Biochem Biophys Res Commun, 257, 79, 10.1006/bbrc.1999.0255

Hotta, 2000, Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients, Arterioscler Thromb Vasc Biol, 20, 1595, 10.1161/01.ATV.20.6.1595

Steppan, 2001, The hormone resistin links obesity to diabetes, Nature, 409, 307, 10.1038/35053000

Lazar, 2002, Resistin and obesity-associated insulin resistance, Trends Endocrinol Metab, 13, 18, 10.1016/S1043-2760(01)00522-7

Savage, 2001, Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-γ action in humans, Diabetes, 50, 2199, 10.2337/diabetes.50.10.2199

Wang, 2002, Human resistin gene. molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians, J Clin Endocrinol Metab, 87, 2520, 10.1210/jcem.87.6.8528

Krakoff, 2003, Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian, Diabetes Care, 26, 1745, 10.2337/diacare.26.6.1745

Yang, 2002, Synthetic peroxisome proliferator activated receptor-γ agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients, Diabetes Care, 25, 376, 10.2337/diacare.25.2.376

Scherer, 1995, A novel serum protein similar to C1q, produced exclusively in adipocytes, J Biol Chem, 270, 26746, 10.1074/jbc.270.45.26746

Hunter, 1998, Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system, Am J Med, 105, 331, 10.1016/S0002-9343(98)00300-3

Rajala, 2003, Adipose-derived resistin and gut-derived resistin-like molecule-β selectively impair insulin action on glucose production, J Clin Invest, 111, 225, 10.1172/JCI16521

McTernan, 2002, Increased resistin gene and protein expression in human abdominal adipose tissue, J Clin Endocrinol Metab, 87, 2407, 10.1210/jcem.87.5.8627

Vidal-Puig, 2001, Resistin: a new link between obesity and insulin resistance?, Clin Endocrinol (Oxf ), 55, 437, 10.1046/j.1365-2265.2001.01377.x

McTernan, 2002, Resistin, central obesity, and type 2 diabetes, Lancet, 359, 46, 10.1016/S0140-6736(02)07281-1

McTernan, 2002, Depot-specific expression of resistin in human adipose tissue and regulation of resistin secretion by insulin and rosiglitazone in human subcutaneous adipocytes in vitro, Diabetologia, 45, A66

Bajaj, 2004, Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type 2 diabetic patients, Internat J Obesity, 28, 783, 10.1038/sj.ijo.0802625

Haugen, 2001, Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes, FEBS Lett, 507, 105, 10.1016/S0014-5793(01)02968-4

Hartman, 2002, Mechanisms regulating adipocyte expression of resistin, J Biol Chem, 277, 19754, 10.1074/jbc.M201451200

Shojima, 2002, Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells, Diabetes, 51, 1737, 10.2337/diabetes.51.6.1737

Saye, 1989, Angiotensinogen gene expression in 3T3-L1 cells, Am J Physiol, 256, C448, 10.1152/ajpcell.1989.256.2.C448

Karlsson, 1998, Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II, J Clin Endocrinol Metab, 83, 3925

Hainault, 2002, Adipose tissue-specific increase in angiotensinogen expression and secretion in the obese (fa /fa) Zucker rat, Am J Physiol, 282, E59

Hsueh, 1999, Insulin signaling in the arterial wall, Am J Cardiol, 84, 21J, 10.1016/S0002-9149(99)00353-7

Goetze, 1999, Troglitazone inhibits angiotensin II-induced extracellular signal-regulated kinase 1/2 nuclear translocation and activation in vascular smooth muscle cells, FEBS Lett, 452, 277, 10.1016/S0014-5793(99)00624-9

Yudkin, 1999, Abnormalities of coagulation and fibrinolysis in insulin resistance. Evidence for a common antecedent?, Diabetes Care, 22, C25

Juhan-Vague, 1997, PAI-I, obesity, insulin resistance and risk of cardiovascular events, Thromb Haemost, 78, 656, 10.1055/s-0038-1657607

Alessi, 1997, Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease, Diabetes, 46, 860, 10.2337/diab.46.5.860

Alessi, 2000, Plasminogen activator inhibitor 1, transforming growth factor-β1, and BMI are closely associated in human adipose tissue during morbid obesity, Diabetes, 49, 1374, 10.2337/diabetes.49.8.1374

Birgel, 2000, Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes, Arterioscler Thromb Vasc Biol, 20, 1682, 10.1161/01.ATV.20.6.1682

Ryden, 2002, Mapping of early signaling events in tumor necrosis factor-α-mediated lipolysis in human fat cells, J Biol Chem, 277, 1085, 10.1074/jbc.M109498200

Hotamisligil, 1993, Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance, Science, 259, 87, 10.1126/science.7678183

Feinstein, 1993, Tumor necrosis factor-α suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates, J Biol Chem, 268, 26055, 10.1016/S0021-9258(19)74276-8

Hotamisligil, 1996, IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance, Science, 271, 665, 10.1126/science.271.5249.665

Hotamisligil, 1995, Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance, J Clin Invest, 95, 2409, 10.1172/JCI117936

Miyazaki, 2003, Tumor necrosis factor α and insulin resistance in obese type 2 diabetic patients, Int J Obesity, 27, 88, 10.1038/sj.ijo.0802187

Nilsson, 1998, Relation between plasma tumor necrosis factor-_and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus, Arterioscler Thromb Vasc Biol, 18, 1199, 10.1161/01.ATV.18.8.1199

Zinman, 1999, Circulating tumor necrosis factor-α concentrations in a native Canadian population with high rates of type 2 diabetes mellitus, J Clin Endocrinol Metab, 84, 272

Spiegelman, 1998, PPAR-gamma: adipogenic regulator and thiazolidinedione receptor, Diabetes, 47, 507, 10.2337/diabetes.47.4.507

Mohamed-Ali, 1997, Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo, J Clin Endocrinol Metab, 82, 4196

Van Snick, 1990, Interleukin 6: an over-view, Annu Rev Immunol, 8, 253, 10.1146/annurev.iy.08.040190.001345

Sandler, 1990, Interleukin-6 affects insulin secretion and glucose metabolism of rat pancreatic islets in vitro, Endocrinology, 126, 1288, 10.1210/endo-126-2-1288

Pradhan, 2001, C-Reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus, JAMA, 286, 327, 10.1001/jama.286.3.327

Pickup, 2000, Plasma interleukin-6, tumour necrosis factor and blood cytokine production in type 2 diabetes, Life Sci, 67, 291, 10.1016/S0024-3205(00)00622-6

Zhang, 1994, Positional cloning of the mouse obese gene and its human homologue, Nature, 372, 425, 10.1038/372425a0

Halaas, 1995, Weight-reducing effects of the plasma protein encoded by the obese gene, Science, 269, 543, 10.1126/science.7624777

Montague, 1998, Depot-related gene expression in human subcutaneous and omental adipocytes, Diabetes, 47, 1384, 10.2337/diabetes.47.9.1384

Ceddia, 1999, Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation, Int J Obesity Related Metab Disord, 23, 75, 10.1038/sj.ijo.0800762

Kamohara, 1997, Acute stimulation of glucose metabolism in mice by leptin treatment, Nature, 389, 374, 10.1038/38717

Muoio, 2002, Peripheral metabolic actions of leptin, Best Prac Res Clin Endocrinol Metab, 16, 653, 10.1053/beem.2002.0223

Ranganathan, 1998, Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin action in adipose and muscle cells, Endocrinology, 139, 2509, 10.1210/endo.139.5.5980

Mantzoros, 2000, Editorial: leptin as a therapeutic agent-trials and tribulations, J Clin Endocrinol Metab, 85, 4000

Clement, 1998, A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction, Nature, 392, 398, 10.1038/32911

Farooqi, 1999, Effects of recombinant leptin therapy in a child with congenital leptin deficiency, N Engl J Med, 341, 879, 10.1056/NEJM199909163411204

Gainsford, 1996, Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells, Proc Natl Acad Sci USA, 93, 14564, 10.1073/pnas.93.25.14564

Fernandes, 1978, Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays, J Clin Invest, 61, 243, 10.1172/JCI108933

Chandra, 1980, Cell-mediated immunity in genetically obese C57BL/6J ob/ob mice, Am J Clin Nutr, 33, 13, 10.1093/ajcn/33.1.13

Choy, 1992, Adipsin and an endogenous pathway of complement from adipose cells, J Biol Chem, 267, 12736, 10.1016/S0021-9258(18)42338-1

Cianflone, 1999, Acylation stimulating protein (ASP), an adipocyte autocrine: new directions, Semin Cell Dev Biol, 10, 31, 10.1006/scdb.1998.0272

Maslowska, 1999, Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations, Eur J Clin Invest, 29, 679, 10.1046/j.1365-2362.1999.00514.x

Mudaliar, 2001, New oral therapies for type 2 diabetes mellitus: the glitazones or insulin sensitizers, Annu Rev Med, 52, 239, 10.1146/annurev.med.52.1.239

Fonseca, 1998, Troglitazone monotherapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled study. The Troglitazone Study Group, J Clin Endocrinol Metab, 83, 3169

Saltiel, 1996, Thiazolidinediiones in the treatment of insulin resistance in type 2 diabetes, Diabetes, 45, 1661, 10.2337/diab.45.12.1661

Aronoff, 1996, Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group, Diabetes Care, 23, 1605, 10.2337/diacare.23.11.1605

Wolffenbuttel, 2001, Rosiglitazone, Expert Opin Pharmacother, 2, 467, 10.1517/14656566.2.3.467

Miyazaki, 2001, Improved glycemic control and enhanced insulin sensitivity in liver and muscle in type 2 diabetic subjects treated with pioglitazone, Diabetes Care, 24, 710, 10.2337/diacare.24.4.710

Miyazaki, 2002, Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients, J Clin Endocrinol Metab, 87, 2784, 10.1210/jcem.87.6.8567

Miyazaki, 2001, Effect of rosiglitazone on glucose and free fatty acid metabolism in type 2 diabetic patients, Diabetologia, 44, 2210, 10.1007/s001250100031

Inzucchi, 1998, Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus, N Engl J Med, 338, 867, 10.1056/NEJM199803263381303

Maggs, 1998, Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial, Ann Intern Med, 128, 176, 10.7326/0003-4819-128-3-199802010-00002

Olfesky, 2000, Treatment of insulin resistance with peroxisome proliferator-activated receptor γ agonists, J Clin Invest, 106, 467, 10.1172/JCI10843

Kim, 2002, Troglitazone but not metformin restores insulinstimulated phosphoinositide 3-kinase activity and increases, p. 110b protein levels in skeletal muscle of type 2 diabetic subjects, Diabetes, 51, 443, 10.2337/diabetes.51.2.443

Mayerson, 2002, The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes, Diabetes, 51, 797, 10.2337/diabetes.51.3.797

Miyazaki, 2002, Dose-response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes mellitus, Diabetes Care, 25, 517, 10.2337/diacare.25.3.517

Berkowitz, 1996, Effect of troglitazone on insulin sensitivity and pancreatic β-cell function in women at high risk for NIDDM, Diabetes, 45, 1572, 10.2337/diab.45.11.1572

Finegood, 2001b, β-Cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death, Diabetes, 50, 1021, 10.2337/diabetes.50.5.1021

Higa, 1999, Troglitazone prevents mitochondrial alterations, βcell destruction, and diabetes in obese prediabetic rats, Proc Natl Acad Sci USA, 96, 11513, 10.1073/pnas.96.20.11513

Willson, 2000, The PPARs: from orphan receptors to drug discovery, J Med Chem, 43, 527, 10.1021/jm990554g

Berger, 2002, The mechanisms of action of PPARs, Annu Rev Med, 53, 409, 10.1146/annurev.med.53.082901.104018

Saad, 2004, Ragaglitazar Dose-Ranging Study Group. Ragaglitazar improves glycemic control and lipid profile in type 2 diabetic subjects: a 12-week, double-blind, placebo-controlled dose-ranging study with an open pioglitazone arm, Diabetes Care, 27, 1324, 10.2337/diacare.27.6.1324

Ren, 2002, PPARγ knockdown by engineered transcription factors: exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis, Genes Dev, 16, 27, 10.1101/gad.953802

Tontonoz, 1994, Stimulation of adipogenesis in fibroblasts by P, PAR_2, a lipid-activated transcription factor, Cell, 79, 1147, 10.1016/0092-8674(94)90006-X

Rosen, 1999, PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro, Mol Cell, 4, 611, 10.1016/S1097-2765(00)80211-7

Hallakou, 1997, Pioglitazone induces in vivo adipocyte differentiation in obese Zucker fa /fa rats, Diabetes, 46, 1393, 10.2337/diabetes.46.9.1393

Ribon, 1998, Thiazolidinediones and insulin resistance: peroxisome proliferator-activated receptor γ activation stimulates expression of the CAP gene, Proc Natl Acad Sci USA, 95, 14751, 10.1073/pnas.95.25.14751

Mori, 1999, Effects of troglitazone on body fat distribution in type 2 diabetic patients, Diabetes Care, 22, 908, 10.2337/diacare.22.6.908

Kelley, 1999, Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes, Diabetes Care, 22, 288, 10.2337/diacare.22.2.288

Kawai, 1999, Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes, Metabolism, 48, 1102, 10.1016/S0026-0495(99)90122-1

Gastaldelli, 2000, Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans: a quantitative study, Diabetes, 49, 1367, 10.2337/diabetes.49.8.1367

Jacobs, 1999, Hearing H-U. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects, Diabetes, 48, 1113, 10.2337/diabetes.48.5.1113

Martin, 1996, Effects of acute and chronic exercise on fat metabolism, Exercise Sport Sci Rev, 24, 203, 10.1249/00003677-199600240-00009

Abernethy, 1990, Acute and chronic responses of skeletal muscle to endurance and sprint exercise, A Rev Sports Med, 10, 365, 10.2165/00007256-199010060-00004

Kelley, 2002, Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes, Diabetes, 51, 2944, 10.2337/diabetes.51.10.2944

Itani, 2002, Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha, Diabetes, 51, 2005-, 10.2337/diabetes.51.7.2005

Ellis, 2000, Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle, Amj Physiol, 279, E554

Mora, 2002, An adipocentric view of signaling and intracellular trafficking, Diabetes Metab Res Rev, 18, 345, 10.1002/dmrr.321

Song, 2002, Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules, Biochem Biophy Res Commun, 299, 291, 10.1016/S0006-291X(02)02551-2

Fonseca, 1998, Effect of troglitazone on fibrinolysis and activated coagulation in patients with non-insulin-dependent diabetes mellitus, J Diabetes Complications, 12, 181, 10.1016/S1056-8727(97)00109-8

Yu, 2002, The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects, Diabetes, 51, 2968, 10.2337/diabetes.51.10.2968

Sreenan, 1996, Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone, Am J Physiol, 271, E742

Smith, 2000, Rosiglitazone prevent the onset of hyperglycemia and proteinuria in the Zucker diabetic fatty rat, Diabetes Obesity Metab, 2, 363, 10.1046/j.1463-1326.2000.00099.x

Finegood, 2001, Beta-Cell mass dynamics in Zucker diabetic fatty rats: rosiglitazone prevents the rise in net cell death, Diabetes, 50, 1021, 10.2337/diabetes.50.5.1021

Lupi, 2002, PPARγ ligand-specificity in the modulation of insulin release from isolated human islets in response to fatty acid incubation, Diabetologia, 45, A161

Marselli, 2002, Rosiglitazone partially prevents free fatty acid-induced cytotoxicity of human pancreatic islet cells, Diabetologia, 45, A161

Buchanan, 2002, Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women, Diabetes, 51, 2796, 10.2337/diabetes.51.9.2796

Cavaghan, 1997, Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance, J Clin Invest, 100, 530, 10.1172/JCI119562