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Recent studies using magnetic resonance spectroscopy have shown that decreased insulin-stimulated muscle glycogen synthesis due to a defect in insulin-stimulated glucose transport activity is a major factor in the pathogenesis of type 2 diabetes. The molecular mechanism underlying defective insulin-stimulated glucose transport activity can be attributed to(More)
To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2 diabetes (IR offspring), we measured mitochondrial content by electron microscopy and insulin signaling in muscle biopsy samples obtained from these individuals(More)
In order to investigate the role of mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) in the pathogenesis of hepatic steatosis and hepatic insulin resistance, we examined whole-body insulin action in awake mtGPAT1 knockout (mtGPAT1(-/-)) and wild-type (wt) mice after regular control diet or three weeks of high-fat feeding. In(More)
Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of(More)
2-Amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2- aminodipyrido [1,2-a:3',2'-d]imidazole, potent mutagens from glutamic acid pyrolysate, were given orally to CDF1 mice of both sexes at concentrations of 0.05% in pellet diet. 2-Amino-3-methyl-9H-pyrido[2,3-b]indole and 2-amino-9H-pyrido[2,3-b]indole, potent mutagens from soybean globulin pyrolysate,(More)
Large-scale clinical studies have shown that n-3 polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic and docosahexaenoic acids reduce cardiovascular events without improving classical risk factors for atherosclerosis. Recent studies have proposed that direct actions of n-3 PUFAs themselves, or of their enzymatic metabolites, have antioxidative(More)
Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and(More)
Recent studies have suggested that n-3 fatty acids, abundant in fish oil, protect against high-fat diet-induced insulin resistance through peroxisome proliferator-activated receptor (PPAR)-alpha activation and a subsequent decrease in intracellular lipid abundance. To directly test this hypothesis, we fed PPAR-alpha null and wild-type mice for 2 weeks with(More)
The transcription factor farnesoid X receptor (FXR) has recently been implicated in the control of hepatic triglyceride production. Activation of FXR may ameliorate hypertriglyceridemia, a cardinal feature of the metabolic syndrome. Because hamsters share many characteristic features of human lipid metabolism, we used a high-fructose-fed hamster model to(More)
Nonalcoholic fatty liver disease (NAFLD) is a major contributing factor to hepatic insulin resistance in type 2 diabetes. Diacylglycerol acyltransferase (Dgat), of which there are two isoforms (Dgat1 and Dgat2), catalyzes the final step in triglyceride synthesis. We evaluated the metabolic impact of pharmacological reduction of DGAT1 and -2 expression in(More)