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Glucagon, in Concert with Insulin, Supports the Postabsorptive Plasma Glucose Concentration in Humans

¹From the Divisions of Endocrinology, Metabolism and Lipid Research and of Geriatrics and Nutritional Science (B.W.P.), Washington University School of Medicine, St. Louis, Missouri, 63110, U.S.A

Correspondence: pcryer{at}wustl.edu

Key Words: Glucoregulation • Hypoglycemia • Glucagon • Insulin • Pancreatic (Islet) Clamp

Objective:Given interest in glucagon antagonism as a potential treatment of diabetes, we tested the hypothesis that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.

Research Design and Methods:Following preliminary studies which indicated that a peripheral intravenous insulin dose of 0.1 mU·kg^-1·min.^-1 (lower than those used previously) provides basal insulin replacement and that a glucagon dose of 1.0 ng·kg^-1·min.^-1 under-replaces basal glucagon, we infused the somatostatin analogue octreotide (30 ng·kg^-1·min.^-1) (with growth hormone replacement) over four hours in 14 healthy adults on four separate occasions to produce endogenous insulin and glucagon deficiency with: 1) saline (combined insulin and glucagon deficiency), 2) insulin replacement (isolated glucagon deficiency), 3) partial glucagon replacement (insulin and partial glucagon deficiency), and 4) insulin and partial glucagon replacement (partial glucagon deficiency).

Results:During combined insulin and glucagon deficiency glucose production decreased and then increased and mean (±SE) plasma glucose decreased from 83±1 mg/dL to 63±2 mg/dL at 60 min. and then increased to 89±3 mg/dL at 240 min. During isolated glucagon deficiency plasma glucose decreased to hypoglycemic levels and was 55±2 mg/dL at 240 min. (P<0.0001 v. combined insulin and glucagon deficiency). Partial glucagon replacement raised plasma glucose to higher levels (P=0.0469) during insulin deficiency and to higher levels (P=0.0090) during insulin replacement.

Conclusions:These three findings provide direct evidence that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.

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