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) ( approximately 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.
Wallis
Michelle G
MG
Department of Biochemistry, Medical School, University of Tasmania, Hobart, 7001 Tasmania, Australia.
Wheatley
Catherine M
CM
Rattigan
Stephen
S
Barrett
Eugene J
EJ
Clark
Andrew D H
AD
Clark
Michael G
MG
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply*; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D014970:Xanthines / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D014970:Xanthines; C053085:1-methylxanthine