INSULINOTROPIC HORMONE GLUCAGON-LIKE PEPTIDE-1-(7-37) APPEARS NOT TO AUGMENT INSULIN-MEDIATED GLUCOSE-UPTAKE IN YOUNG MEN DURING EUGLYCEMIA

Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormon e that augments insulin secretion in response to meals and lowers bloo d glucose levels in both type 1 and type 2 diabetic subjects. It has b een proposed that a substantial component of the glucose-lowering effe cts of GLP-1 occurs via insulin-independent mechanisms. However, the i nterpretations of the studies have been controversial. This study was conducted to examine whether glucagon-like peptide (GLP-1) has an insu lin-like effect during euglycemia. Nine young lean men (age, 25 +/- 1. 4 yr; body mass index, 24.0 +/- 0.7 kg/m(2)) volunteered to participat e in two euglycemic clamp studies (n = 18 clamps) for 120 min. The ini tial clamp was performed with a primed continuous infusion of GLP-1 at a final rate of 1.5 pmol/kg.min from 0-60 min. At 60 min, the GLP-1 i nfusion was terminated, and euglycemia was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was mea sured. A second study was performed that was identical to the first, w ith the infusion of regular insulin in place of GLP-1. Insulin infusio n rates were designed in each individual to simulate plasma insulin le vels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Basal plasma insulin levels w ere similar between studies and averaged 49 +/- 5 pmol/L. Basal GLP-1 levels were also similar (6.0 +/- 1.0 pmol/L). In response to the GLP- 1 infusion, although basal plasma glucose levels were clamped, signifi cant increases in insulin occurred in all subjects (P < 0.001). With t he nearly identical plasma insulin levels during the two studies (30-6 0 min levels: GLP-1 study, 151 +/- 48; insulin study, 146 +/- 31 pmol/ L), the rate of disappearance of glucose progressively increased in re sponse to both GLP-1 and insulin infusions, but was not significantly different between the studies. The design of the study necessitated co nducting the GLP-1 study first, which may have been accompanied by a g reater stress than the second study. We, therefore, measured cortisol levels. Basal cortisol land ACTH) levels were not different. However, cortisol levels significantly increased during the GLP-1 infusions, an d this was preceded by an increase in ACTH levels. Somatostatin levels were not different either basally or during the clamps. We conclude t hat in the euglycemic state, an acute infusion of GLP-1 does not have insulinlike effects in lean nondiabetic men. Intravenous administratio n of GLP-1 activates hypothalamic neuroendocrine neurons.