Insulin secretion and clearance during low-dose graded glucose infusion.
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)
Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637.
M M
MM
Byrne
J
J
Sturis
K S
KS
Polonsky
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005260:Female; D005502:Food; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D008297:Male
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose