Insulin-Mediated Hemodynamic Changes Are Impaired in Muscle of Zucker Obese Rats
Wallis, MG and Wheatley, C and Rattigan, S and Barrett, EJ and Clark, ADH and Clark, MG, Insulin-Mediated Hemodynamic Changes Are Impaired in Muscle of Zucker Obese Rats, Diabetes, 51, (12) pp. 3492-3498. ISSN 0012-1797 (2002) [Refereed Article]
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 × 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 (∼5.6-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.