Effects of Somatostatin and Adrenergic Blockade on Glucagon, Insulin and Glucose in Exercising Sheep

Abstract

The mechanisms of hyperglycemia in exercising sheep were characterized. Sheep were run on a treadmill for 45 min (5.5 km h-1, 8% incline) during adrenergic blockade (propranolol or phentolamine mesylate infusions) and during suppression of the rise in glucagon by infusion of somatostatin (SRIF). Propranolol did not alter the glucagon, insulin or glucose responses, except it tended to increase the metabolic clearance of glucose, presumably as a result of blocking the .beta.-adrenergic inhibition of glucose uptake. Phentolamine mesylate administration was associated with a suppression of the rise in glucagon concentrations, a reversal of .alpha.-adrenergic inhibition of insulin release and a reduction in glucose appearance during exercise. SRIF prevented the rise in glucagon and reduced insulin concentrations to below resting values. Propranolol and phentolamine mesylate did not alter the glucagon, insulin or glucose responses to SRIF. SRIF prevented the insulin rise that occurred during phentolamine administration. The increment in glucose appearance produced in response to exercise was the same for SRIF, SRIF plus phentolamine mesylate and phentolamine mesylate in the first 25 min of exercise, but was significantly less than in the controls. During the last 20 min of exercise, glucose appearance was not significantly different from the control for any of the groups. The depression by SRIF and .alpha.-adrenergic blockade of the increment in glucose appearance due to exercise was associated with an impairment of the glucagon response. Glucagon may stimulate glucose production early in exercise in sheep directly, and by having a permissive effect.