Observation of Insulin Resistance in Skeletal Muscle in an In Situ Perfused Hindquarter Preparation

Abstract

The hypothesis that insulin resistance in obesity results from a reduction in glucose transport activity was tested studying obese female ddymice six weeks after the administration of gold thioglucose (GTG 800 mg/kg). Glucose uptake was studied by measuring the 2-deoxyglucosephosphate (2 DGP) accumulation after tritiumlabeled 2 DG infusion in lean and in obese mice, in both the basal and the insulin-stimulated states, using a perfused hindquarter preparation. Hexokinase activity in a skeletal muscle from the hindquarter was also studied by measuring the nicotinamideadenosine dinucleotide phosphate, (NADPH), production using the method of Berger. The 2 DGP accumulation rate in obese mice was significantly reduced not only in the insulin-stimulated state but also in the basal state. 2 DGP is not metabolised further, so a reduced 2 DGP accumulation suggest that the glucose transport activity or the hexokinase activity is reduced in the obese mice. Contrary to the 2 DGP accumulation, the hexokinase activity of obese mice did not differ from that of lean mice (lean: 5.0±1.1μmol/min/mg protein, obese: 5.2±0.2μmol/min/mg protein). These results suggest that reduced glucose transport activity plays a role in insulin resistance in the skeletal muscle of gold thioglucose-induced obese mice.