INSULIN-SECRETION AND CLEARANCE DURING LOW-DOSE GRADED GLUCOSE-INFUSION

The present study was undertaken in normal volunteers to define the al terations in beta-cell responsiveness to glucose associated with diffe rent physiological states, including fasting and refeeding, and after prolonged intravenous glucose infusion. A low-dose graded glucose infu sion protocol was used to explore the dose-response relationship betwe en glucose and insulin secretion. Studies were performed in 10 normal volunteers, and insulin secretion rates (ISR) were calculated by decon volution of peripheral C-peptide levels using a two-compartment model utilizing individual kinetic parameters. From 5 to 9 mmol/l glucose, t he relationship between glucose and ISR was linear. After a 42-h gluco se infusion at a rate of 4 mg.kg-1.min-1, the ISR increased by 53% ove r the same glucose concentration range (P < 0.002), resulting in a shi ft of the dose-response curve to the left. Insulin clearance rates dec reased 27% after the 42-h glucose infusion (P < 0.001). After a 72-h f ast, ISR decreased by 32% from baseline over the 5-8 mmol/l glucose ra nge (P = 0.056), resulting in a shift of the dose-response curve to th e 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 increase d by 31% after refeeding compared with the baseline study (P < 0.05). These approaches thus allow alterations in the glucose responsiveness of the beta-cell brought about by glucose infusion, fasting, and refee ding to be detected and should allow early defects in beta-cell functi on to be defined in states of glucose intolerance.