ACUTE INCRETIN RESPONSE TO ORAL GLUCOSE IS ASSOCIATED WITH STIMULATION OF GASTRIC-INHIBITORY POLYPEPTIDE, NOT GLUCAGON-LIKE PEPTIDE IN YOUNG SUBJECTS

Oral glucose induces a greater insulin response than i.v. glucose, a d ifference apparently due to the secretion of gut factors (''incretins' '). Studies examining the mechanisms of this finding in human subjects are limited, however, because of differences in glucose profiles. To overcome this obstacle, we studied eight young nonobese subjects using the hyperglycemic clamp with and without superimposed ingestion of or al glucose. In both studies, glucose was acutely raised by 125 mg/dL a bove fasting values by the infusion of i.v. glucose and maintained at this level for 180 min. During the experimental study, but not the con trol, each subject ingested oral glucose (30 g) at 120 min, and the gl ucose infusion was adjusted to maintain the plasma glucose plateau. Pl asma insulin responses were nearly identical during both studies until oral glucose was added. After oral glucose, both plasma insulin and C -peptide levels sharply increased by 45-55% above control values (p < 0.001), indicating a potentiation of insulin secretion rather than dec reased hepatic extraction of insulin. Plasma gastric inhibitory polype ptide (GIP) levels increased significantly in response to oral glucose , whereas plasma levels of glucagon-like peptide-1(7-37) were not affe cted. The time course of the the in plasma GIP and insulin was nearly identical. We conclude that the GIP response to a modest oral glucose load may play an important physiologic role in glucose-stimulated insu lin secretion in healthy young subjects.