New Concepts in Glucagon Physiology

A decreased renal clearance of glucagon contributes to the hyperglucagonemia of uremia and of starvation. Thus, hyperglucagonemia does not necessarily reflect altered glucagon secretion. Experimental hyperglucagonemia produced in normal human subjects by means of intravenous infusions of glucagon resulted in fleeting elevations of splanchnic glucose production and blood glucose level. No changes in glucose tolerance were noted, even though there was no compensatory hyperinsulinism. The IV administration of glucagon in physiologic doses to insulin-treated diabetic patients did not alter the level of blood glucose and ketone bodies, or the urinary excretion of glucose and nitrogen, but caused marked hyperglycemia in insulin-deprived juvenile diabetics. Prolonged infusions of somatostatin cause temporary hypoglycemia followed by hyperglycemia. The latter is due to suppression of insulin secretion and occurs despite the concomitant persistent suppression of glucagon. Thus, basal glucagon secretion is not essential for the development of fasting hyperglycemia in diabetes and hyperglucagonemia worsens the diabetic state only when insulin is not available. The results underscore the primary role of insulin deficiency rather than glucagon excess in the pathogenesis of diabetes and suggest that by further suppressing insulin secretion, somatostatin may worsen metabolic control in adult-onset diabetic patients.