Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.
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It is concluded that, during hyperinsulinemia, lipid promptly replaced carbohydrate as fuel for oxidation in muscle and hours later inhibited glucose uptake, presumably by interfering with muscle glycogen formation.Abstract:
We have examined the onset and duration of the inhibitory effect of an intravenous infusion of lipid/heparin on total body carbohydrate and fat oxidation (by indirect calorimetry) and on glucose disappearance (with 6,6 D2-glucose and gas chromatography-mass spectrometry) in healthy men during euglycemic hyperinsulinemia. Glycogen synthase activity and concentrations of acetyl-CoA, free CoA-SH, citrate, and glucose-6-phosphate were measured in muscle biopsies obtained before and after insulin/lipid and insulin/saline infusions. Lipid increased insulin-inhibited fat oxidation (+40%) and decreased insulin-stimulated carbohydrate oxidation (-63%) within 1 h. These changes were associated with an increase (+489%) in the muscle acetyl-CoA/free CoA-SH ratio. Glucose disappearance did not decrease until 2-4 h later (-55%). This decrease was associated with a decrease in muscle glycogen synthase fractional velocity (-82%). The muscle content of citrate and glucose-6-phosphate did not change. We concluded that, during hyperinsulinemia, lipid promptly replaced carbohydrate as fuel for oxidation in muscle and hours later inhibited glucose uptake, presumably by interfering with muscle glycogen formation.read more
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TLR4 links innate immunity and fatty acid–induced insulin resistance
TL;DR: It is suggested that TLR4 is a molecular link among nutrition, lipids, and inflammation and that the innate immune system participates in the regulation of energy balance and insulin resistance in response to changes in the nutritional environment.
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Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
TL;DR: Continuously elevated levels of plasma FFAs may play a key role in the pathogenesis of NIDDM in predisposed individuals by impairing peripheral glucose utilization and by promoting hepatic glucose overproduction.
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Mechanism of free fatty acid-induced insulin resistance in humans.
Michael Roden,Thomas B. Price,Gianluca Perseghin,Kitt Falk Petersen,Douglas L. Rothman,Gary W. Cline,Gerald I. Shulman +6 more
TL;DR: It is demonstrated that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.
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Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α
TL;DR: The results indicated that the insulin resistance observed in human muscle when plasma FFA levels were elevated during euglycemic-hyperinsulinemic clamping was associated with increases in DAG mass and membrane-associated PKC-betaII and -delta and a decrease in IkappaB-alpha.
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Mechanisms of Insulin Action and Insulin Resistance
TL;DR: This work aims to develop an integrated physiological perspective, placing the intricate signaling effectors that carry out the cell-autonomous response to insulin in the context of the tissue-specific functions that generate the coordinated organismal response.
References
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The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.
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The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization
TL;DR: The results suggest that the ability of higher doses of insulin to further stimulate glucose metabolism is primarily the result of increased glucose storage by peripheral tissues, most likely muscle.
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Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by 13C Nuclear Magnetic Resonance Spectroscopy
Gerald I. Shulman,Douglas L. Rothman,Thomas Jue,Peter J. Stein,Ralph A. DeFronzo,Robert G. Shulman +5 more
TL;DR: It is concluded that muscle glycogen synthesis is the principal pathway of glucose disposal in both normal and diabetic subjects and that defects in muscle glycogens synthesis have a dominant role in the insulin resistance that occurs in persons with NIDDM.
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A rapid filter paper assay for UDPglucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP-14C-glucose.
TL;DR: A modified method for enzymic synthesis of UDP-14C-glucose in high yield is described, and it was found that stopping the transferase-catalyzed reaction by precipitation of trichloroacetic acid insoluble protein resulted in a loss of radioactive glucose.