Mechanism of troglitazone action in type 2 diabetes - PubMed (original) (raw)

Mechanism of troglitazone action in type 2 diabetes

K F Petersen et al. Diabetes. 2000 May.

Abstract

To examine the metabolic pathways by which troglitazone improves insulin responsiveness in patients with type 2 diabetes, the rate of muscle glycogen synthesis was measured by 13C-nuclear magnetic resonance (NMR) spectroscopy. The rate-controlling steps of insulin-stimulated muscle glucose metabolism were assessed using 31P-NMR spectroscopic measurement of intramuscular glucose-6-phosphate (G-6-P) combined with a novel 13C-NMR method to assess intracellular glucose concentrations. Seven healthy nonsmoking subjects with type 2 diabetes were studied before and after completion of 3 months of troglitazone (400 mg/day) therapy. After troglitazone treatment, rates of insulin-stimulated whole-body glucose uptake increased by 58+/-11%, from 629+/-82 to 987+/-156 micromol x m(-2) x min(-1) (P = 0.008), which was associated with an approximately 3-fold increase in rates of insulin-stimulated glucose oxidation (from 119+/-41 to 424+/-70 micromol x m(-2) x min(-1); P = 0.018) and muscle glycogen synthesis (26+/-17 vs. 83+/-35 micromol x l(-1) muscle x min(-1); P = 0.025). After treatment, muscle G-6-P concentrations increased by 0.083+/-0.019 mmol/l (P = 0.008 vs. pretreatment) during the hyperglycemic-hyperinsulinemic clamp, compared with no significant changes in intramuscular G-6-P concentrations in the pretreatment study, reflecting an improvement in glucose transport and/or hexokinase activity. The concentrations of intracellular free glucose did not differ between the pre- and posttreatment studies and remained >50-fold lower in concentration (<0.1 mmol/l) than what would be expected if hexokinase activity was rate-controlling. These results indicate that troglitazone improves insulin responsiveness in skeletal muscle of patients with type 2 diabetes by facilitating glucose transport activity, which thereby leads to increased rates of muscle glycogen synthesis and glucose oxidation.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources