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Insulin-Glucagon Interaction in Controlling Splanchnic Glucose Production in Norma Man

J. D. BOMBOY, JR.^*, S. B. LEWIS, B. C. SINCLAIR-SMITH, W. W. LACY and J. E. LILJENQUIST

Veterans Administration Hospital, Nashville, Tennessee, and Department of Medicine, Vanderbilt University School of Medicine Nashville, Tennessee

Address reprints requests to: Dr. J. D. Bomboy, Jr., Veterans Administration Hospital, 1310 24th Avenue South, Nashville, Tennessee 37203.

The interaction of glucagon and insulin in controlling hepatic glucose production in man has been inferred from studies of immunoreactive glucagon and insulin. This study directly examines the interaction of glucagon and insulin in controlling net splanchnic glucose production (NSGP) in eight normal men. Glucagon was infused iv at 5 µg/kg/min for 15 min and resultantarterial glucagon levels (1.3 x ^–10M) did not exceed the physiologic portalrange. In four normal men NSGPincreased 2.3- fold by 5 min and remained elevated for 15 min. Therewas no change in arterial insulin concentration.

To study the effect of exogenous insulin on this glucagon-induced increase in NSGP, insulin was infused at 10 mU/kg/min in four normal men to achieve arterial immunoreactive insulin concentrations of 1500 µU/ml (1 x 10^–8M). Blood glucose was stabilized by glucose infusions. During insulin and glucose administration, NSGP was suppressed and net splanchnic glucose uptakeoccurred. After 40 min of insulinand glucose pretreatment, a 5 ng/kg/min glucagon infusion resulted in no increase in NSGP (arterial insulin: glucagon molar ratio of approximately 100). In two subjects the glucagon infusion rate was then increased to 15 ng/kg/min (arterial insulin: glucagon molar ratio of approximately 33), resulting in stimulation of NSGP.

These studies provide evidence that insulin in high concentration can suppress glucagon-stimulated NSGP in normal man.

Supported by the Veterans Administration and NIH Grant HL08195.

^* Research Associate, Veterans Administration Hospital, MRIS #1019.

Investigator of the Howard Hughes Medical Institute.

This work appeared, in part, in abstract form in J Clin Invest 52: 37a, 1973.

Received June 11, 1976.

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