Lipid Infusion Impairs Physiologic Insulin-Mediated Capillary Recruitment and Muscle Glucose Uptake In Vivo
Infusion of triglycerides and heparin causes insulin resistance in muscle. Because the vascular actions of insulin, particularly capillary recruitment, may contribute to the increase in glucose uptake by skeletal muscle, we investigated the effects of Intralipid/heparin infusion on the hemodynamic actions of insulin during clamp conditions. Saline or 10% Intralipid/heparin (33 U/ml) was infused into anesthetized rats at 20 μl/min for 6 h. At 4 h into the saline infusion, a 2-h hyperinsulinemic (3 mU · min−1 · kg−1)-euglycemic clamp was conducted (Ins group). At 4 h into the lipid infusion, a 2-h saline control (Lip group) or 2-h hyperinsulinemic-euglycemic clamp (Lip + Ins group) was conducted. Arterial blood pressure, heart rate, femoral blood flow (FBF), hindleg vascular resistance, glucose infusion rate (GIR), hindleg glucose uptake (HGU), and muscle 2-deoxyglucose uptake (R′g) were measured. Capillary recruitment, as measured by metabolism of infused 1-methylxanthine (1-MX), was also assessed. When compared with either Lip or Lip + Ins, Ins had no effect on arterial blood pressure, heart rate, FBF, or vascular resistance but increased GIR, HGU, and R′g of soleus, plantaris, extensor digitorum longus, and gastrocnemius red muscles and hindlimb 1-MX metabolism. GIR, HGU, and R′g of soleus, plantaris, gastrocnemius red, and the combined muscles and 1-MX metabolism were less in Lip + Ins than in Ins rats. HGU correlated closely with hindleg capillary recruitment (r = 0.86, P < 0.001) but not total hindleg blood flow. In conclusion, acute elevation of plasma free fatty acids blocks insulin-mediated glucose uptake and capillary recruitment.
Address correspondence and reprint requests to Michael G. Clark, Biochemistry, School of Medicine, University of Tasmania, GPO Box 252-58, Hobart, Tasmania, Australia, 7001. E-mail:.
Received for publication 15 August 2001 and accepted in revised form 17 December 2001.
1-MX, 1-methylxanthine; 2DG, 2-deoxyglucose; eNOS, endothelial nitric oxide synthase; FBF, femoral arterial blood flow; HGU, hindleg glucose uptake; IMGU, insulin-mediated glucose uptake; PKCθ, protein kinase Cθ; R′g, muscle 2DG uptake; TNF, tumor necrosis factor; XO, xanthine oxidase.