Acute Insulin Responses to Intravenous Glucose and GLP-1 are Independent of Preceding High-frequency Insulin Pulse-defects Induced by Glucose Entrainment in Healthy Humans

Abstract

The objective of this study was to test the hypothesis that high-frequency oscillations in insulin release is a part of the mechanistic basis of a prompt and adequate insulin response to iv-glucose and GLP-1 exposure. In ten healthy subjects, five different insulin release patterns were induced for 360 min using computer-based glucose infusion (glucose delivered in a constant, a regular pulsatile, an irregular pulse frequency, an irregular pulse amplitude or a regular but very fast-pulsatile manner) in healthy subjects. The amount of glucose infused was identical in all five protocols (24 mg/kg/h). After 360 min, insulin secretion was assessed by means of a first-phase insulin secretion test (25 g glucose) and injection of GLP-1 (9 microg). By frequent blood sampling and analysis of insulin concentration, glucose-induced entrainment was evident in all protocols except in the constant infusion and the very fast-pulse protocol. The first-phase insulin release to glucose and GLP-1-induced insulin release were, however, comparable in the protocols. We therefore conclude from this short-term experimental setting in healthy subjects that beta-cell response to either iv-glucose or GLP-1 is independent of the preceding regularity of oscillations in insulin release.

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

“…Insulin and C-peptide delivery from the splanchnic bed was measured in the basal overnight-fasted state and then during a constant glucose infusion of 2 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 by concurrent sampling from the hepatic vein and an arterialized hand vein catheter. The constant glucose infusion rather than a hyperglycemic clamp was selected to avoid induction of spurious insulin pulses arising from fluctuations in glucose infusion rate (26,27). Splanchnic blood flow was measured by indocyanine green infusion.…”

“…Written informed consent was obtained from all study participants. Five healthy subjects (two men and three women) mean age 32 years (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], with a mean BMI of 24.9 kg/m 2 (21.2-27.1) participated. All subjects were nondiabetic based on fasting plasma glucose concentration (mean fasting plasma glucose 5.4 mmol/l [5.1-5.8]) and HbA 1c values (mean 4.8% [4.5-5.0]).…”