AJP - Endocrinology and Metabolism, Vol 268, Issue 1 E21-E27, Copyright © 1995 by American Physiological Society

ARTICLES

Insulin secretion and clearance during low-dose graded glucose infusion

M. M. Byrne, J. Sturis and K. S. Polonsky
Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637.

The present study was undertaken in normal volunteers to define the alterations in beta-cell responsiveness to glucose associated with different physiological states, including fasting and refeeding, and after prolonged intravenous glucose infusion. A low-dose graded glucose infusion protocol was used to explore the dose-response relationship between glucose and insulin secretion. Studies were performed in 10 normal volunteers, and insulin secretion rates (ISR) were calculated by deconvolution of peripheral C-peptide levels using a two-compartment model utilizing individual kinetic parameters. From 5 to 9 mmol/l glucose, the relationship between glucose and ISR was linear. After a 42-h glucose infusion at a rate of 4 mg.kg-1.min-1, the ISR increased by 53% over the same glucose concentration range (P < 0.002), resulting in a shift of the dose-response curve to the left. Insulin clearance rates decreased 27% after the 42-h glucose infusion (P < 0.001). After a 72-h fast, ISR decreased by 32% from baseline over the 5-8 mmol/l glucose range (P = 0.056), resulting in a shift of the dose-response curve to the right. This shift was reversed by a 42-h period of refeeding, after which ISR was increased by 77% compared with the fasting study (P < 0.02). Refeeding enhanced the beta-cell responsiveness, and ISR increased by 31% after refeeding compared with the baseline study (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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