EFFECTS OF TRUNCATED GLUCAGONLIKE PEPTIDE-1 ON PANCREATIC HORMONE-RELEASE IN NORMAL CONSCIOUS DOGS

The effects of truncated glucagon-like peptide-1 (GLP-1) on insulin and glucagon release were examined in unanesthetized normal dogs. A bolus injection of GLP-1(7-36) amide elicited a transient increase in the plasma insulin level, which brought about a decrease in the plasma glucose level. The degree of increase in plasma insulin levels with GLP-1(7-35) OH or GLP-1(7-37)OH was less than that induced by GLP-1(7-36) amide. The plasma glucagon level did not increase in spite of mild hypoglycemia. The infusion of graded doses of GLP-1(7-36) amide (6, 36, 120 ng. kg-1 . min-1 every 30 min) did not change the plasma glucose, insulin or glucagon levels significantly. The degree of increase in the plasma glucose level induced by iv glucose infusion (12 mg . kg -1 . min-1) was reduced by coinfusion of GLP-1(7-36)amide (6 ng. kg-1. min-1), although the degree of increase in the plasma insulin level was the same as that in a control experiment (coinfusion of the vehicle). Coinfusion of GLP-1(7-36) amide (60 ng . kg-1 . min-1) caused an augmented increase in the plasma insulin level and a reduced increased in the plasma glucose level during iv glucose infusion (17 mg . kg-1 . min-1) compared with the control experiment. The degree of decrease in the plasma glucagon level during iv glucose infusion was not affected by the coinfusion. The degree of increase in the plasma glucagon level induced by insulin hypoglycemia and the profile of the plasma glucose level at that time were not affected by the infusion of GLP-1(7-36) amide. These results demonstrate that 1. the insulinotropic activity of GLP-1(7-36) amide is higher than that of GLP-1(7-37)OH or GLP-1(7-35)OH; 2. GLP-1(7-36) amide suppresses the degree of increase in plasma glucose level during iv glucose infusion by augmented insulin release, and 3. the glucagonostatic activity of truncated GLP-1 is negligible under physiological conditions.