INTERACTION OF INSULIN, GLUCAGON-LIKE PEPTIDE-1, GASTRIC-INHIBITORY POLYPEPTIDE, AND APPETITE IN RESPONSE TO INTRADUODENAL CARBOHYDRATE

The relation between gastrointestinal incretin hormones in the control of insulin release and short-term satiety by intestinal carbohydrate was investigated in 8 fasted, healthy male volunteers. Insulin, gastri c inhibitory polypeptide (GIP), glucagon-Iike peptide 1 (GLP-1), and a ppetite ratings were measured during, and food intake was measured aft er, intraduodenal infusions of glucose or saline. Studies were conduct ed under hyperinsulinemic and euglycemic conditions. Raising plasma in sulin with intravenous insulin infusion to concentrations slightly abo ve usual postprandial concentrations (356.4 +/- 3.8 pmol/L) had no eff ect on GIP, GLP-1, or appetite ratings before the intraduodenal infusi ons began. Intraduodenal glucose infusion resulted in a further increa se in plasma insulin to a peak of 779.4 +/- 114.0 pmol/L, caused an ea rly increase in plasma GIP and a later increase in GLP-1 concentration s (P < 0.01), suppressed appetite (P < 0.05), and reduced energy intak e (P < 0.01) compared with intraduodenal infusion of saline. There was a close association between the increase in GLP-1 and decrease in app etite. Infusion of octreotide to suppress the release of gastrointesti nal hormones prevented the rise in insulin, GIP, and GLP-1 induced by intraduodenal glucose infusion and reversed the suppression of appetit e and reduction in energy intake. These results suggest that 1) when i nfused to result in plasma concentrations slightly above usual postpra ndial concentrations, insulin does not inhibit its own release and 2) the effects of intraduodenal glucose on appetite may be mediated throu gh the release of GLP-1 and not insulin.