Mechanism of impaired insulin-stimulated muscle glucose metabolism in subjects with insulin-dependent diabetes mellitus.

摘要: To determine the mechanism of impaired insulin-stimulated muscle glycogen metabolism in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM), we used 13C-NMR spectroscopy to monitor peak intensity C1 resonance glucosyl units during a 6-h hyperglycemic-hyperinsulinemic clamp using [1-(13)C]glucose-enriched infusate followed by nonenriched glucose. Under similar steady state (t = 3-6 h) plasma glucose (approximately 9.0 mM) and insulin concentrations 400 pM), nonoxidative was significantly less IDDM subjects compared age-weight-matched control (37+/-6 vs. 73+/-11 micromol/kg body wt per minute, P < 0.05), which could be attributed an approximately 45% reduction net rate synthesis (108+/-16 195+/-6 micromol/liter 0.001). Muscle turnover than that controls (16+/-4 33+/-5%, indicating marked flux through synthase responsible for reduced subjects. 31P-NMR intramuscular concentration glucose-6-phosphate (G-6-P) under same conditions. Basal G-6-P between two groups 0.10 mmol/kg muscle) but increment response glucose-insulin infusion 50% (0.07+/-0.02 0.13+/-0.02 muscle, 0.05). When metabolic rates were matched subjects, (0.06+/-0.02 no different Together, these data indicate defective transport/phosphorylation is major factor lower diabetic