To determine the importance of the fall in insulin on whole body glucose fluxes and muscle glucose metabolism during exercise, dogs ran on a motorized treadmill for 90 min at a moderate work rate with somatostatin (SRIF) infused to suppress insulin and glucagon and basal (B-INS; n = 6 dogs) or exercise-stimulated (S-INS; n = 8 dogs) insulin replacement. The fall in insulin during exercise potently stimulates glucose production at least in part by potentiating the actions of glucagon. To assess the hepatic effects of insulin in the absence of its potentiating effect on glucagon action, glucagon levels were not restored during SRIF infusion. At least 17 days before experimentation, dogs underwent surgery for chronic placement of sampling (carotid artery and femoral vein) and infusion (inferior vena cava and portal vein) catheters. Hindlimb blood flow was assessed by placement of a Doppler flow cuff on the external iliac artery. Whole body glucose production (Ra) and disappearance (Rd) were assessed with [3-3H]glucose, and hindlimb glucose uptake and metabolism were assessed with arterial-venous differences and [U-14C]glucose. Insulin levels were 69 +/- 6 and 61 +/- 7 pM at rest in B-INS and S-INS and 62 +/- 10 and 41 +/- 6 pM at 30 min of exercise. Glucose levels were clamped at euglycemic levels with an exogenous glucose infusion during rest and exercise in both groups. Exercise-induced increases in Ra, Rd, hindlimb glucose uptake, and hindlimb oxidative and nonoxidative glucose metabolism were not affected by maintenance of basil insulin levels during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)