Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes

Endocrine Reviews

Volumn 23, Issue 2, 2002, Pages 201-229

  Lewis, Gary F ^a   Carpentier, André ^a   Adeli, Khosrow ^a   Giacca, Adria ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID; GLUCOSE; INSULIN;

ADIPOSE TISSUE; CALORIC INTAKE; CELL FUNCTION; CONTROLLED STUDY; DIABETOGENESIS; DISEASE COURSE; DYSLIPIDEMIA; ENERGY BALANCE; ENVIRONMENTAL FACTOR; FATTY ACID TRANSPORT; FATTY LIVER; GLUCOSE METABOLISM; GLUCOSE TOLERANCE TEST; HEREDITY; HUMAN; HUMAN TISSUE; HYPERINSULINEMIA; HYPERTRIGLYCERIDEMIA; INSULIN CLEARANCE; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID METABOLISM; LIPIDOSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS ISLET BETA CELL; PATHOGENESIS; PHYSICAL ACTIVITY; POSTPRANDIAL STATE; PRIORITY JOURNAL; REVIEW; SEQUENCE ANALYSIS; TISSUE DISTRIBUTION;

EID: 0036217052     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/edrv.23.2.0461     Document Type: Review

References (445)

1. The hormone resistin links obesity to diabetes
2. Obesity and insulin resistance
3. Diet and Syndrome X
4. Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans
5. Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations
6. Adipose tissue metabolism in obesity: Lipase action in vivo before and after a mixed meal
7. Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities
8. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM
9. Diabetes mellitus in the Pima Indians: Incidence, risk factors and pathogenesis
10. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM
11. The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: Results of the Paris Prospective Study
12. Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes
13. Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients: Is cellular insulin resistance a secondary phenomenon?
14. 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
15. Metabolic defects in lean nondiabetic offspring of NIDDM parents: A cross-sectional study
16. The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation
17. Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men
18. Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia
19. Influence of obesity on the antilipolytic effect of insulin in isolated human fat cells obtained before and after glucose ingestion
20. Fat metabolism in human obesity
21. Influence of body fat distribution on free fatty acid metabolism in obesity
22. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance
23. Effect of short-term fasting on lipid kinetics in lean and obese women
24. Insulin regulation of glucose and lipid metabolism in massive obesity
25. The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus
26. Glycerol production in subcutaneous adipose tissue in lean and obese humans
27. Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects
28. Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity
29. Insulin regulation of plasma free fatty acid concentrations is abnormal in healthy subjects with muscle insulin resistance
30. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance
31. Effect of insulin on glycerol production in obese adolescents
32. Plasma free fatty acid turnover rate in obesity
33. The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents
34. Insulin resistance with respect to lipolysis in non-diabetic relatives of European patients with type 2 diabetes
35. Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin
36. Enhanced escape of non-esterified fatty acids from tissue uptake: Its role in impaired insulin-induced lowering of total rate of appearance in obesity and type II diabetes mellitus
37. Lipolytic response to glucose infusion in human subjects
38. Effects of insulin on human adipose tissue metabolism in vivo
39. Regulation of free fatty acid metabolism by insulin in humans: Role of lipolysis and reesterification
40. Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition
41. Net carbon flux across subcutaneous adipose tissue after a standard meal in normal-weight and insulin-resistant obese subjects
42. Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism
43. Postprandial triglyceride response in type 1 (insulin-dependent) diabetes mellitus is not altered by short-term deterioration in glycaemic control or level of postprandial insulin replacement
44. Triglyceride synthesis: Insights from the cloning of diacylglycerol acyltransferase
45. Enhancement of microsomal phosphatidate phosphohydrolase and diacylglycerol acyltransferase activity by insulin during growth of rat adipocyte precursors in culture
46. Lipoprotein lipase and the disposition of dietary fatty acids
47. Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans
48. Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non-insulin-dependent diabetes mellitus
49. Insulin responsiveness of adipose tissue lipoprotein lipase is delayed but preserved in obesity
50. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
51. How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids?
52. The fatty acid transport function of fatty acid-binding proteins
53. Role of CD36 in membrane transport and utilization of long-chain fatty acids by different tissues
54. Reversible binding of long-chain fatty acids to purified FAT, the adipose CD36 homolog
55. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats
56. CD36, insulin resistance, and coronary heart disease
57. Defective uptake and utilization of long-chain fatty acids in muscle and adipose tissues of CD36 knockout mice
58. Defective fatty acid uptake in the spontaneously hypertensive rat is a primary determinant of altered glucose metabolism, hyperinsulinemia and myocardial hypertrophy
59. Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats
60. Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin
61. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism
62. CD36 deficiency associated with insulin resistance
63. CD36 mediates long-chain fatty acid transport in human myocardium: Complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog in subjects with CD36 deficiency
64. Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents
65. Adipocyte metabolism in adipocyte fatty acid binding protein knockout mice (aP2-/-) after short-term high-fat feeding: Functional compensation by the keratinocyte fatty acid binding protein
66. Fatty acid transport proteln-1 mRNA expression in skeletal muscle and in adipose tissue in humans
67. Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice
68. Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice
69. Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations
70. The effect of ASP on the adipocyte of the morbidly obese
71. Treatment of obesity: Need to focus on high risk abdominally obese patients
72. The perils of portliness: Causes and consequences of visceral adiposity
73. Visceral fat and insulin resistance-causative or correlative?
74. Relationship of anterior and posterior subcutaneous abdominal fat to insulin sensitivity in nondiabetic men
75. Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM
76. Quantification of adipose tissue by MRI: Relationship with anthropometric variables
77. Adipose tissue distribution measured by magnetic resonance imaging in obese women
78. The hepatic circulation
79. Postprandial mesenteric blood flow in humans: Relationship to endogenous gastrointestinal hormone secretion and energy content of food
80. Familial partial lipodystrophy: A monogenic form of the insulin resistance syndrome
81. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
82. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: Model for congenital generalized lipodystrophy
83. Mechanism of insulin resistance in A-ZIP/F-1 fatless mice
84. Cellular mechanisms of insulin resistance
85. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30
86. Surgical treatment of obesity and its effect on diabetes: 10-yr follow-up
87. Influence of human obesity on the metabolic fate of dietary long- and medium-chain triacylglycerols
88. Enhanced dietary fat clearance in postobese women
89. Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats
90. Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
91. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
92. Improved glucose and lipid metabolism in genetically obese mice lacking aP2
93. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue
94. Amelioration of insulin resistance in streptozotocin diabetic mice by transgenic overexpression of GLUT4 driven by an adipose-specific promoter
95. Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects
96. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat
97. Skeletal muscle triglyceride levels are inversely related to insulin action
98. Intramuscular glycogen and intramyocellular lipid utilization during prolonged exercise and recovery in man: A 13C and 1H nuclear magnetic resonance spectroscopy study
99. Muscle structure with low- and high-fat diets in well-trained male runners
100. Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance
101. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss
102. Markers of capacity to utilize fatty acids in human skeletal muscle: Relation to insulin resistance and obesity and effects of weight loss
103. Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: Studies with PET and 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid
104. Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle
105. Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise
106. Lipid oxidation is reduced in obese human skeletal muscle
107. Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects
108. Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats
109. Fatty acid oxidation and the regulation of malonyl-CoA in human muscle
110. Malonyl-CoA content and fatty acid oxidation in rat muscle and liver in vivo
111. The effect of an increased free fatty acid concentration on thermogenesis and substrate oxidation in obese and lean men
112. Body composition and energy expenditure after weight loss following bariatric surgery
113. Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise
114. Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism
115. Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria
116. Glucose and insulin-induced inhibition of fatty acid oxidation: The glucose-fatty acid cycle reversed
117. Mechanisms of cellular uptake of long chain free fatty acids
118. Interaction between glucose and free fatty acid metabolism in human skeletal muscle
119. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus
120. Skeletal muscle utilization of free fatty acids in women with visceral obesity
121. 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
122. The insulin sensitizer, BRL 49653, reduces systemic fatty acid supply and utilization and tissue lipid availability in the rat
123. Reversal of chronic alterations of skeletal muscle protein kinase C from fat-fed rats by BRL-49653
124. Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects
125. A review of intestinal fatty acid binding protein gene variation and the plasma lipoprotein response to dietary components
126. An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance
127. Association between Ala54Thr substitution of the fatty acid-binding protein 2 gene with insulin resistance and intra-abdominal fat thickness in Japanese men
128. Type 2 diabetes mellitus: Association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism
129. The A54T polymorphism at the intestinal fatty acid binding protein 2 is associated with insulin resistance in glucose tolerant Caucasians
130. Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects
131. Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects
132. Codon 54 polymorphism of the fatty acid binding protein gene and insulin resistance in the Japanese population
133. Variants of the insulin receptor substrate-1 and fatty acid binding protein 2 genes and the risk of type 2 diabetes, obesity, and hyperinsulinemia in African-Americans: The Atherosclerosis Risk in Communities Study
134. Intestinal fatty acid binding protein polymorphism at codon 54 is not associated with postprandial responses to fat and glucose tolerance tests in healthy young Europeans. Results from EARS II participants
135. Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans
136. Postprandial lipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene
137. Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene
138. Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men
139. Diseases of liporegulation: New perspective on obesity and related disorders
140. Lipotoxic diseases of nonadipose tissues in obesity
141. Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia
142. Comparing the hypothalamic and extrahypothalamic actions of endogenous hyperleptinemia
143. Direct antidiabetic effect of leptin through triglyceride depletion of tissues
144. Reversing adipocyte differentiation: Implications for treatment of obesity
145. Increased lipogenic capacity of the islets of obese rats: A role in the pathogenesis of NIDDM
146. Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes
147. Etiology of the metabolic syndrome: Potential role of insulin resistance, leptin resistance, and other players
148. Plasma leptin levels after biliopancreatic diversion: Dissociation with body mass index
149. Development of leptin resistance in rat soleus muscle in response to high-fat diets
150. Fatty acids inhibit leptin signalling in BRIN-BD11 insulinoma cells
151. Downregulation of leptin by free fatty acids in rat adipocytes: Effects of triacsin C, palmitate, and 2-bromopalmitate
152. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
153. Diabetes mellitus: A thrifty genotype rendered detrimental by progress?
154. Fuel selection in human skeletal muscle in insulin resistance: A reexamination
155. Diabetes mellitus in the Pima Indians: Genetic and evolutionary considerations
156. Triglyceride-rich lipoproteins in diabetes
157. Hypertriglyceridernia and its metabolic consequences as a risk factor for atherosclerotic cardiovascular disease in non-insulin-dependent diabetes mellitus
158. HDL metabolism in hypertriglyceridemic states. An overview
159. Fatty acid regulation of very low density lipoprotein (VLDL) production
160. Lipid metabolism of rat liver isolated and perfused in hypoxia
161. Turnover and splanchnic metabolism of free fatty acids and ketones in insulin-dependent diabetics at rest and in response to exercise
162. Hepatic metabolism of free fatty acids in normal and diabetic dogs
163. The 75-g oral glucose tolerance test: Effect on splanchnic metabolism of substrates and pancreatic hormone release in healthy man
164. Effect of stress hormones on splanchnic substrate and insulin disposal after glucose ingestion in healthy humans
165. Nonhepatic response to portal glucose delivery in conscious dogs
166. Changes in availability of glucogenic and ketogenic substrates and liver metabolism in fed or starved rats
167. Gut and liver fat metabolism in depancreatized dogs: Effects of exercise and acute insulin infusion
168. Intracellular degradation of newly synthesized apolipoprotein B
169. Synthesis and secretion of apolipoprotein B from cultured liver cells
170. Insulin regulation of triacylglycerolrich lipoprotein synthesis and secretion
171. Secretion of apolipoprotein B-containing lipoproteins from HeLa cells is dependent on expression of the microsomal triglyceride transfer protein and is regulated by lipid availability
172. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia
173. The role of pancreatic hormones in the regulation of lipid storage, oxidation and secretion in primary cultures of rat hepatocytes. Short- and long-term effects
174. Secretion of lipids, apolipoproteins, and lipoproteins by human hepatoma cell line, HepG2: Effects of oleic acid and insulin
175. Regulation of apo B secretion from HepG2 cells: Evidence for a critical role for cholesteryl ester synthesis in the response to a fatty acid challenge
176. The apolipoprotein B gene is constitutively expressed in HepG2 cells: Regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life
177. Interaction of non-esterified fatty acid and insulin in control of triacylglycerol secretion by Hep G2 cells
178. Control of Hep G2-cell triacylglycerol and apolipoprotein B synthesis and secretion by polyunsaturated non-esterified fatty acids and insulin
179. Oleate stimulates secretion of apolipoprotein B-containing lipoproteins from Hep G2 cells by inhibiting early intracellular degradation of apolipoprotein B
180. Oleate-mediated stimulation of apolipoprotein B secretion from rat heparoma cells. A function of the ability of apolipoprotein B to direct lipoprotein assembly and escape presecretory degradation
181. Extracellular fatty acids are not utilized directly for the synthesis of very-low-density lipoprotein in primary cultures of rat hepatocytes
182. Serum factors influencing cultured hepatocyte exogenous and endogenous triglyceride
183. Studies on intracellular translocation of apolipoprotein B in a permeabilized HepG2 system
184. Studies on the assembly of apo B-100-containing lipoproteins in HepG2 cells
185. Intracellular degradation in the regulation of secretion of apolipoprotein B-100 by rabbit hepatocytes
186. Effects of fatty acids on apolipoprotein B secretion by McArdle RH-7777 rat hepatoma cells
187. Intrahepatic assembly of very low density lipoprotein. Competition by Cholesterol esters for the hydrophobic core
188. Effect of fatty acids on lipid and apoprotein secretion and association in hepatocyte cultures
189. Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster
190. Differential effects of eicosapentaenoic acid on glycerolipid and apolipoprotein B metabolism in primary human hepatocytes compared to HepG2 cells and primary rat hepatocytes
191. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans
192. Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans
193. Precursors of plasma triglyceride fatty acids in obesity
194. Role of human liver lipogenesis and reesterification in triglycerides secretion and in FFA reesterification
195. Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance
196. Chronic exogenous insulin and carbohydrate supplementation increase de novo VLDL triglyceride fatty acid production in rats
197. Decreased sensitivity to the inhibitory effect of insulin on the secretion of very-low-density lipoprotein in cultured hepatocytes from fructose-fed rats
198. VLDL output by hepatocytes from obese Zucker rats is resistant to the inhibitory effect of insulin
199. Chronic exogenous hyperinsulinaemia does not modify the acute inhibitory effect of insulin on the secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B in primary cultures of rat hepatocytes
200. Fatty acid synthetase activity in the liver and adipose tissue of rats fed with various carbohydrates
201. In vivo effects of hyperinsulinemia on lipogenic enzymes and glucose transporter expression in rat liver and adipose tissues
202. ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose
203. Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes
204. Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice
205. Measurement of de novo hepatic lipogenesis in humans using stable isotopes
206. Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection
207. Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia hyperinsulinemia in normal man
208. Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet
209. Carbohydrate-induced hypertriacylglycerolemia: Historical perspective and review of biological mechanisms
210. The enzymology of hepatic very-low-density lipoprotein assembly
211. Malonyl-CoA and carnitine palmitoyltransferase I: An expanding partnership
212. The mitochondrial carnitine palmitoyltransferase system: Its broadening role in fuel homoeostasis and new insights into its molecular features
213. Secretion and storage of newly synthesized hepatic triacylglycerol fatty acids in vivo in different nutritional states and in diabetes
214. Effect of nutritional state on the utilization of fatty acids for hepatitic triacylglycerol synthesis and secretion as very-low-density lipoprotein
215. Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion
216. Mobilisation of triacylglycerol stores
217. The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas
218. Intracellular triacylglycerol lipase: Its role in the assembly of hepatic very-low-density lipoprotein (VLDL)
219. Contribution of de novo fatty acid synthesis to very low density lipoprotein triacylglycerols: Evidence from mass isotopomer distribution analysis of fatty acids synthesized from [2H6]ethanol
220. Origin of triacylglycerol moiety of plasma very low density lipoproteins in the rat: Structural studies
221. Use of cytosolic triacylglycerol hydrolysis products and of exogenous fatty acid for the synthesis of triacylglycerol secreted by cultured rat hepatocytes
222. Role of insulin in hepatic fatty acid partitioning: Emerging concepts
223. Non-alcoholic steatohepatitis: Association with obesity and insulin resistance, and influence of weight loss
224. Fatty liver-an additional and treatable feature of the insulin resistance syndrome
225. Role of hyperinsulinemia and glucose intolerance in the pathogenesis of nonalcoholic fatty liver in patients with normal body weight
226. Non-alcoholic steatohepatitis (NASH): A disease of emerging identity and importance
227. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver
228. Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men-role of the metabolic syndrome
229. Non-alcoholic fatty liver: Another feature of the metabolic syndrome?
230. Association of nonalcoholic fatty liver disease with insulin resistance
231. Exogenous VLDL stimulates apolipoprotem B secretion from HepG2 cells by both pre- and post-translational mechanisms
232. Effects of chylomicron remnants and β-VLDL on the class and composition of newly secreted lipoproteins by HepG2 cells
233. Acute effects of insulin in the control of VLDL production in humans
234. Hyperinsulinemia and triglyceride-rich lipoproteins
235. Expression of apolipoprotein B in vitro in cell-free lysates of HepG2 cells: Evidence that insulin modulates ApoB synthesis at the translational level
236. Insulin modulation of human apolipoprotein B mRNA translation: Studies in an in vitro cell-free system from HepG2 cells
237. Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apo B production in normal weight and obese individuals
238. VLDL production is decreased to a similar extent by acute portal vs. peripheral venous insulin
239. Metabolic basis of hypotriglyceridemic effects of insulin in normal men
240. Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in normal subjects
241. Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM
242. Insulin stimulates triacylglycerol secretion by perfused livers from fed rats but inhibits it in livers from fasted or insulin-deficient rats implications for the relationship between hyperinsulinaemia and hypertriglyceridaemia
243. A switch in the direction of the effect of insulin on the partitioning of hepatic fatty acids for the formation of secreted triacylglycerol occurs in vivo, as predicted from studies with perfused livers
244. Use of in vivo and in vitro techniques for the study of the effects of insulin on hepatic triacylglycerol secretion in different insulinaemic states
245. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose
246. Obese Zucker (fa/fa) rats are resistant to insulin's inhibitory effect on hepatic apo B secretion
247. Sensitivity to acute insulin-mediated suppression of fasting plasma free fatty acids is not a determinant of VLDL triglyceride secretion in healthy humans
248. The effect of systemic vs. portal insulin delivery in pancreas transplantation on insulin action and VLDL metabolism
249. Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance. Evidence for enhanced lipoprotein assembly, reduced intracellular apo B degradation, and increased microsomal triglyceride transfer protein in a fructose-fed hamster model
250. Hepatic VLDL-apo B overproduction is associated with attenuated hepatic insulin signaling in a fructose-fed hamster model of insulin resistance: Evidence for increased expression of PTP-1B and decreased abundance of ER-60 protease
251. Hepatic VLDL overproduction and reduced apo B degradation in an animal model of insulin resistance, the fructose-fed hamster, is associated with suppression of intracellular levels of ER-60 protease
252. Apolipoprotein B is intracellularly associated with an ER-60 protease homologue in HepG2 cells
253. Knockout of the abetalipoproteinemia gene in mice: Reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes
254. Adenovirus-mediated overexpression of microsomal triglyceride transfer protein (MTP): Mechanistic studies on the role of MTP in apolipoprotein B-100 biogenesis
255. Sterol regulatory element-binding protein negatively regulates microsomal triglyceride transfer protein gene transcription
256. The glucose-fatty acid cycle: Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus
257. Glucose metabolism in rat skeletal muscle at rest. Effect of starvation, diabetes, ketone bodies and free fatty acids
258. Elevated free fatty acid levels inhibit glucose phosphorylation in slow-twitch rat skeletal muscle
259. Inhibition of glucose uptake and glycogenolysis by availability of oleate in well-oxygenated perfused skeletal muscle
260. Plasma free fatty acids decrease insulin-stimulated skeletal muscle glucose uptake by suppressing glycolysis in conscious rats
261. Effects of FFA on insulin-stimulated glucose fluxes and muscle glycogen synthase activity in rats
262. 13C and 31P NMR studies on the effects of increased plasma free fatty acids on intramuscular glucose metabolism in the awake rat
263. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C θ and alterations in the insulin signaling cascade
264. Role of the glucosamine pathway in fat-induced insulin resistance
265. Free fatty acids impair hepatic insulin extraction in vivo
266. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog
267. Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin
268. Time dependence of the interaction between lipid and glucose in humans
269. Mechanisms of fatty acid-induced inhibition of glucose uptake
270. Effect of fatty acids on glucose production and utilization in man
271. Effect of free fatty acids on glucose uptake and nonoxidative glycolysis across human forearm tissues in the basal state and during insulin stimulation
272. Effect of glycemia and nonesterified fatty acids on forearm glucose uptake in normal humans
273. Does free fatty acid infusion impair insulin action also through an increase in oxidative stress?
274. Mechanism of free fatty acid-induced insulin resistance in humans
275. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity
276. Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans
277. Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo
278. Malonyl-CoA, fuel sensing, and insulin resistance
279. Mechanism of palmityl coenzyme A inhibition of liver glycogen synthase
280. Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects
281. Operation of Randle's cycle in patients with NIDDM
282. Effects of free fatty acids and ketone bodies on in vivo non-insulin-mediated glucose utilization and production in humans
283. Stimulation of hormone-sensitive lipase activity by contractions in rat skeletal muscle
284. Activation of protein kinase C by cis- and trans-octadecadienoic acids in intact human platelets and its potentiation by diacylglycerol
285. Activation of protein kinase C α inhibits signaling by members of the insulin receptor family
286. 2+- and phospholipid-activated protein kinase (protein kinase C)
287. Transgenic mice with inactivation of PKC θ are protected from lipid-induced defects in insulin action and signaling in skeletal muscle
288. Alterations in the expression and cellular localization of protein kinase C isozymes ε and θ are associated with insulin resistance in skeletal muscle of the high-fat-fed rat
289. Cellular mechanism of nutritionally induced insulin resistance in Psammomys obesus: Overexpression of protein kinase C ε in skeletal muscle precedes the onset of hyperinsulinemia and hyperglycemia
290. Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate
291. Association of acyl-CoA synthetase-1 with GLUT4-containing vesicles
292. Free fatty acids induce peripheral insulin resistance without increasing muscle hexosamine pathway product levels in rats
293. A mechanism for fatty acid inhibition of glucose utilization in liver. Role of xylulose 5-P
294. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle
295. Oxidative stress and insulin action: Is there a relationship?
296. Cytosolic triglycerides and oxidative stress in central obesity: The missing link between excessive atherosclerosis, endothelial dysfunction, and β-cell failure?
297. Involvement of glycation and oxidative stress in diabetic macroangiopathy
298. NAC (N-acetylcysteine) prevents hyperglycemia and glucosamine-induced insulin resistance in vitro and in vivo by different mechanisms
299. N-Acetyl-L-cysteine prevents insulin resistance due to glucotoxicity and lipotoxicity in vivo
300. Normalization of diacylglycerol-protein kinase C activation by vitamin E in aorta of diabetic rats and cultured rat smooth muscle cells exposed to elevated glucose levels
301. Increased flux through the hexosamine biosynthesis pathway inhibits glucose transport acutely by activation of protein kinase C
302. Inhibition of IKKβ reverses 'insulin resistance' in cultured cells
303. Prevention of fat-induced insulin resistance by salicylate
304. Reversal of obesity-and diet-induced insulin resistance with salicilates or targeted disruption of Ikkβ
305. A novel role for inducible nitric oxide synthase (inos) in the development of insulin resistance and glucose intolerance in high-fat fed obese mice
306. Polyunsaturated fatty acid regulation of gene transcription: A mechanism to improve energy balance and insulin resistance
307. The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation
308. Unraveling the mechanism of action of thiazolidinediones
309. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs
310. Portal delivery of free fatty acids compared to peripheral delivery has no greater effect on hepatic glucose production but results in greater peripheral hyperinsulinemia
311. In vivo evidence for hepatic autoregulation during FFA-stimulated gluconeogenesis in normal humans
312. The inhibitory effect of free fatty acids on hepatic glycogenolysis in the conscious dog
313. Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans
314. Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes
315. Lipid-dependent control of hepatic glycogen stores in healthy humans
316. Control of hepatic glycogenolysis
317. Contribution of muscle and liver to glucose-fatty acid cycle in humans
318. High plasma free fatty acids decrease splanchnic glucose uptake in patients with non-insulin-dependent diabetes mellitus
319. Role of FFA in regulating postprandial glucose uptake by muscle and liver in the dog
320. In normal men, free fatty acids reduce peripheral but not splanchnic glucose uptake
321. Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps
322. Control mechanisms of gluconeogenesis and ketogenesis. I. Effects of oleate on gluconeogenesis in perfused rat liver
323. Importance of the modulation of glycolysis in the control of lactate metabolism by fatty acids in isolated hepatocytes from fed rats
324. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver
325. Binding and translocation of glucokinase in hepatocytes
326. Control of glucokinase translocation in rat hepatocytes by sorbitol and the cytosolic redox state
327. Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding
328. Hepatic malonyl-CoA levels of fed, fasted and diabetic rats as measured using a simple radioisotopic assay
329. Specific inhibition of glucokinase by long chain acyl coenzymes A below the critical micelle concentration
330. Mechanisms by which fatty-acyl-CoA esters inhibit or activate glucose-6-phosphatase in intact and detergent-treated rat liver microsomes
331. Unsaturated fatty acids activate glycogen phosphorylase in cultured rat hepatocytes
332. Oleic acid promotes changes in the subcellular distribution of protein kinase C in isolated hepatocytes
333. A new antidiabetic agent, BRL 49653, reduces lipid availability and improves insulin action and glucoregulation in the rat
334. Free fatty acids time-dependently impair glucose metabolism by mechanisms unrelated to the Randle cyle
335. Free fatty acid-induced impairment in hepatic glucose metabolism is time-dependent and associated with protein kinase C δ translocation
336. Hexosamine excess in liver results in obesity, hypertriglyceridemia, and glucose intolerance
337. Cyclic AMP and fatty acids increase carnitine palmitoyltransferase I gene transcription in cultured fetal rat hepatocytes
338. Polyunsaturated fatty acid regulation of gene transcription: A mechanism to improve energy balance and insulin resistance
339. Stimulation of phosphoenolpyruvate carboxykinase gene expression by fatty acids
340. Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion
341. Lipotoxic heart disease in obese rats: Implications for human obesity
342. Quantitative study of insulin secretion and clearance in normal and obese subjects
343. Fatty acids in the portal vein of the rat regulate hepatic insulin clearance
344. Effects of free fatty acids and glucose on splanchnic insulin dynamics
345. Acute enhancement of insulin secretion by FFA is lost with prolonged FFA elevation
346. Effects of a 48-h fat infusion on insulin secretion and glucose utilization
347. Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes
348. Receptor and postreceptor effects of free fatty acids (FFA) on hepatocyte insulin dynamics
349. Prevention of inhibitory effect of free fatty acids on insulin binding and action in isolated rat hepatocytes by etomoxir
350. Role of intracellular calcium and protein kinase C in the endocytosis of transferrin and insulin by HL60 cells
351. Oleate-induced decrease in hepatocyte insulin binding is mediated by protein kinase C (PKC) activation
352. Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced β-cell response
353. Are the β-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?
354. Fatty acids, lipotoxicity and insulin secretion
355. Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse β-cells
356. Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect
357. Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects
358. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation
359. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans
360. Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects
361. The role of long-chain fatty acyl-CoA esters in β-cell signal transduction
362. Stimulation of islet protein kinase C translocation by palmitate requires metabolism of the fatty acid
363. Long-chain acyl CoA regulation of protein kinase C and fatty acid potentiation of glucose-stimulated insulin secretion in clonal β-cells
364. Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells)
365. A fatty acid-dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion
366. Transgenic mice with increased hexosamine flux specifically targeted to β-cells exhibit hyperinsulinemia and peripheral insulin resistance
367. A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation
368. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle
369. Palmitate-induced β-cell insensitivity to glucose is coupled to decreased pyruvate dehydrogenase activity and enhanced kinase activity in rat pancreatic islets
370. Defective fatty acid-mediated β-cell compensation in Zucker diabetic fatty rats. Pathogenic implications for obesity-dependent diabetes
371. Fatty acids rapidly induce the carnitine palmitoyltransferase I gene in the pancreatic β-cell line INS-1
372. Chronic effect of fatty acids on insulin release is not through the alteration of glucose metabolism in a pancreatic β-cell line (β HC9)
373. Impaired β-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM
374. Fatty acid inhibition of glucose-stimulated insulin secretion is enhanced in pancreatic islets from insulin-resistant rats
375. Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro
376. Chronic exposure to free fatty acid reduces pancreatic β cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation
377. Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans
378. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications
379. Effect of elevated plasma non-esterified fatty acids (NEFAs) on arginine-stimulated insulin secretion in obese humans
380. Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels
381. Lipid rather than glucose metabolism is implicated in altered insulin secretion caused by oleate in INS-1 cells
382. Long chain coenzyme A esters activate the poreforming subunit (Kir6.2) of the ATP-regulated potassium channel
383. Uncoupling protein 2: A possible link between fatty acid excess and impaired glucose-induced insulin secretion?
384. Interleukin-1 β-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 β-induced inhibition of insulin secretion
385. Ceramide inhibits pancreatic β-cell insulin production and mitogenesis and mimics the actions of interleukin-1 β
386. Glucose-induced pre-proinsulin gene expression is inhibited by the free fatty acid palmitate
387. Long-term elevation of free fatty acids leads to delayed processing of proinsulin and prohormone convertases 2 and 3 in the pancreatic β-cell line MIN6
388. Fatty acid-induced β cell apoptosis: A link between obesity and diabetes
389. Lipoapoptosis in β-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression
390. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants
391. Beneficial effects of antioxidants in diabetes: Possible protection of pancreatic β-cells against glucose toxicity
392. Inhibition of insulin gene expression by long-term exposure of pancreatic β cells to palmitate is dependent on the presence of a stimulatory glucose concentration
393. Lipotoxicity of the pancreatic β cell is associated with glucose-dependent esterification of fatty acids into neutral lipids
394. Long-term exposure of β-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression
395. Glucose down-regulates the expression of the peroxisome proliferator-activated receptor-α gene in the pancreatic β-cell
396. Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis, is expressed and active in β-cells
397. Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion
398. Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats
399. Increased uncoupling protein-2 levels in β-cells are associated with impaired glucose-stimulated insulin secretion: Mechanism of action
400. Adenovirus-mediated overexpression of uncoupling protein-2 in pancreatic islets of Zucker diabetic rats increases oxidative activity and improves β-cell function
401. Quantification of the relationship between insulin sensitivity and β-cell function in human subjects. Evidence for a hyperbolic function
402. Lipid infusion lowers sympathetic nervous activity and leads to increased β-cell responsiveness to glucose
403. Lowering fatty acids potentiates acute insulin response in first degree relatives of people with type II diabetes
404. Prolonged elevation of plasma free fatty acids impairs pancreatic β-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes
405. A prolonged elevation of plasma free fatty acids desensitises the insulin secretory response to glucose in vivo in rats
406. The composition of dietary fat profoundly influences insulin secretion in normal rats
407. Prolonged elevation of free fatty acids (FFA) impairs the β cell compensatory response to insulin resistance in obese and prediabetic rats
408. The lipotoxic effect of free fatty acids on glucose stimulated insulin secretion is accentuated in prediabetic diabetes-prone BB rats
409. N-Acetylcysteine prevents the lipotoxic effect of fatty acids on glucose-stimulated insulin secretion in vivo
410. Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release
411. Unsaturated fatty acids alter the insulin secretion response of the islets of Langerhans in vitro
412. Electrogenic arginine transport mediates stimulus-secretion coupling in mouse pancreatic β-cells
413. L-Arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide
414. Inhibition of lipolysis by nicotinic acid and by acipimox
415. Mechanism of anti-lipolytic action of acipimox in isolated rat adipocytes
416. Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM
417. Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects
418. Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus
419. Effects of prolonged acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus
420. Reversal of steroid-induced insulin resistance by a nicotinic-acid derivative in man
421. Effect of acute inhibition of lipolysis on operation of the glucose-fatty acid cycle in hepatic cirrhosis
422. Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus
423. Different acute and chronic effects of acipimox treatment on glucose and lipid metabolism in patients with type 2 diabetes
424. Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects
425. Inhibition of lipolysis stimulates whole body glucose production and disposal in normal postabsorptive subjects
426. Effect of decreasing plasma free fatty acids by acipimox on hepatic glucose metabolism in normal rats
427. Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients
428. Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans
429. Effects of cholestyramine and acipimox on subfractions of plasma low density lipoprotein. Studies in normolipidaemic and hypercholesterolaemic subjects
430. Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM
431. Pronounced blood glucose-lowering effect of the antilipolytic drug acipimox in noninsulin-dependent diabetes mellitus patients during a 3-day intensified treatment period
432. Long-term effects of a sustained-release preparation of acipimox on dyslipidemia and glucose metabolism in non-insulin-dependent diabetes mellitus
433. The effect of acipimox in patients with type 2 diabetes and persistent hyperlipidaemia
434. A double blind study of the effect of acipimox on serum lipids, blood glucose control and insulin action in non-obese patients with type 2 diabetes mellitus
435. Improvement of lipoprotein lipid composition in type II diabetic patients with concomitant hyperlipoproteinemia by acipimox treatment. Results of a multicenter trial
436. Acipimox attenuates hypertriglyceridemia in dyslipidemic noninsulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control
437. Treatment of hyperlipidaemia with acipimox
438. Effects of acipimox on serum lipids, lipoproteins and lipolytic enzymes in hypertriglyceridemia
439. Acipimox in the treatment of patients with hyperlipidaemia: A double blind trial
440. Reduced triglyceridemia and increased high density lipoprotein cholesterol levels after treatment with acipimox, a new inhibitor of lipolysis
441. Comparison of the effects of bezafibrate and acipimox on the lipid pattern and plasma fibrinogen in hyperlipidaemic type 2 (non-insulin-dependent) diabetic patients
442. A comparative study of policosanol vs. acipimox in patients with type II hypercholesterolemia
443. Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: Effect of acipimox therapy
444. Comparative study of acipimox and pravastatin in patients with combined hyperlipidemia
445. The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia