Effect of Glucagon on Glucose Turnover and Plasma Free Fatty Acids in Depancreatized Dogs Maintained on Matched Insulin Infusions

Abstract

It has been shown previously that glucagon can increase the turnover of glucose in normal dogs and can enhance the secretion of insulin. The aim of this study was to determine the metabolic effects of glucagon independent of the effects of the insulin it releases directly through an action on β cells, and indirectly through hyperglycemia. Eight conscious dogs which could not mobilize extra insulin were obtained by replacing the endogenous insulin secretion of each with an equivalent intraportal infusion of the hormone immediately following removal of a remnant pancreatic autograft. Such infusions (200 μU/kg-min) maintained normal plasma concentrations of glucose and free fatty acids (FFA), as well as normal tracer-determined rates of glucose appearance (Ra) and disappearance (Rd) prior to glucagon infusion.There was a highly significant regression of the increments in glucose production on the rate of glucagon infusion (1.00–3.00 μg/kg-h). Rd increased proportionally to glucose levels, and there was therefore no significant change in the metabolic clearance of glucose. Hence a direct inhibitory effect of glucagon on glucose utilization could not be demonstrated. Corrections for recycling of the infused label did not appreciably affect the observed changes in Ra or Rd. Glucagon infusions did not increase the FFA level in plasma; when hyperglycemia was prominent a small decrease occurred. The role of glucagon in the net release of FFA from adipocytes in dogs is therefore questioned.