Defective non-insulin-mediated and insulin-mediated glucose transport and metabolism in adipocytes from obese and lean patients with untreated type 2 diabetes mellitus.

Abstract

Insulin binding, glucose transport, and glucose metabolism were investigated in isolated adipocytes from 11 lean and 13 obese patients with non-insulin-dependent diabetes mellitus. Insulin binding at 15 degrees C was reduced by 35% (p less than 0.01) in both lean and obese diabetic patients, whereas insulin binding (or uptake) at 37 degrees C was similar in diabetic patients and healthy controls. In lean diabetic patients both non-insulin-mediated (basal) and maximally insulin-stimulated glucose transport and metabolism were significantly reduced (all p less than 0.01). The percentage responses to insulin were also markedly reduced (p less than 0.05, p less than 0.02). In obese diabetic patients basal glucose transport was reduced (p less than 0.01) but basal glucose metabolism was not. Insulin-stimulated glucose transport and metabolism were significantly reduced (p less than 0.01, p less than 0.05). The percentage responses were reduced compared to healthy controls (p less than 0.05, p less than 0.05) but higher than in lean diabetic patients (p less than 0.05). We conclude that adipocytes isolated from both lean and obese patients with non-insulin-dependent diabetes mellitus are characterized by severely depressed non-insulin-mediated and insulin-mediated glucose transport and depressed insulin-mediated glucose metabolism. The major defect seems to be a reduced maximal effect of insulin on glucose metabolism, suggesting post-binding and post-transport abnormalities.