Insulin-mediated hemodynamic changes are impaired in muscle of Zucker obese rats

Insulin-mediated hemodynamic effects in muscle were assessed in relation to insulin resistance in obese and lean Zucker rats. Whole-body glucose infusion rate (GIR), femoral blood flow (FBF), hindleg glucose extraction (HGE), hindleg glucose uptake (HGU), 2-deoxyglucose (DG) uptake into muscles of the lower leg (R-g), and metabolism of infused 1-methylxanthine (1-MX) to measure capillary recruitment were determined for isogylcemic (4.8 +/- 0.2 mmol/l, lean; 11.7 +/- 0.6 mmol/l, obese) insulin-clamped (20 mU.min(-1).kg(-1) X 2 h) and saline-infused control anesthetized age-matched (20 weeks) lean and obese animals. Obese rats (445 +/- 5 g) were less responsive to insulin than lean animals (322 +/- 4 g) for GIR (7.7 +/- 1.4 vs. 22.2 +/- 1.1 mg.min(-1).kg(-1), respectively), and when compared with saline-infused controls there was no increase due to insulin by obese rats in FBF, HGE, HGU, and R-g of soleus, plantaris, red gastrocnemius, white gastrocnemius, extensor digitorum longus (EDL), or tibialis muscles. In contrast, lean animals showed marked increases due to insulin in FBF (5.3-fold), HGE (5-fold), HGU (8-fold), and R-g (similar to5.6-fold). Basal (saline) hindleg 1-MX metabolism was 1.5-fold higher in lean than in obese Zucker rats, and insulin increased in only that of the lean. Hindleg 1-MX metabolism in the obese decreased slightly in response to insulin, thus postinsulin lean was 2.6-fold that of the postinsulin obese. We conclude that muscle insulin resistance of obese Zucker rats is accompanied by impaired hemodynamic responses to insulin, including capillary recruitment and FBF.