The role of glucagon in diabetes was studied in four patients with juvenile-type diabetes during continuous insulin infusion and a diet containing 150 g per day of carbohydrate. During insulin alone, plasma glucagon, measured at two-hour intervals, averaged 182±34 pg per milliliter, glucose 269±11 mg per deciliter, glucose excretion 52±8 g per 24 hours, ketone excretion 1.3±0.3 mmol per 24 hours, and urea nitrogen 12±2 g per 24 hours (mean ± S.E.M.). Somatostatin (2 mg per day) lowered glucagon to 60±13 pg per milliliter, glucose to 111 ±17 mg per deciliter, glucose excretion to 1 ±0.7 g per 24 hours, ketone excretion to 0.5±0.2 mmol per 24 hours and urea nitrogen excretion to 8±2 g per 24 hours. Replacement of glucagon raised glucagon to 272±30 pg per milliliter, glucose to 202±20 mg per deciliter, glucose excretion to 14±7 g per 24 hours, ketone excretion to 0.8 mmol per 24 hours and urea nitrogen excretion to 11±2 g per 24 hours. In a subsequent study, similar improvement occurred on a diet of 30 g of carbohydrate daily, when absorption of dietary glucose was negligible. Hyperglucagonemia has an important role in diabetes; its correction reduces diabetic abnormalities to or toward normal. (N Engl J Med 299:433–436, 1978) THE concept that glucagon contributes importantly to the metabolic derangements of human diabetes1 2 3 4 has recently been challenged, largely on the basis of three lines of evidence: that glucagon does not increase diabetic hyperglycemia if insulin is available5; that glucagon-mediated enhancement of hepatic glucose production is evanescent6 7 8 and could not, therefore, be of long-term importance; and that the amelioration of diabetic hyperglycemia induced by somatostatin treatment9 is the consequence not of the glucagon suppression, but rather of reduced absorption of glucose from the gut.10 The first two issues appear to have been resolved. It has recently been shown that diabetic.
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