A role for endogenous prostaglandin E in biphasic pattern of insulin release in humans.

These studies were undertaken to evaluate in humans the possible physiological role of prostaglandins of the E series (PGE) in modulating insulin release and to assess whether endogenous PGE synthesis may account for the biphasic pattern of insulin secretion. We used a square-wave glucose stimulation previously determined to give maximal biphasic insulin release. Infusion of lysine acetylsalicylate to block the synthesis of endogenous PGE increased by twofold total insulin response to glucose and also converted insulin release to a multiphasic pattern. The infusion of exogenous PGE1 (0.2 microgram X kg-1 X min-1) or PGE2 (10 micrograms/min) in addition to lysine acetylsalicylate restored the typical biphasic pattern of insulin release and also decreased total insulin release to values similar to those of control studies. Infusion of either PGE1 or PGE2 in the absence of lysine acetylsalicylate reset insulin secretion to a lower level without altering the kinetics of release. On the basis of these results, it is hypothesized that endogenous PGE released in response to glucose stimulation exert an inhibiting effect on insulin release that becomes biphasic in appearance.

A possible role of gamma-aminobutyric acid in the control of the endocrine pancreas.

This study examines the effect of baclofen, a specific gamma-aminobutyric acid analog which crosses the blood-brain barrier freely, upon insulin, glucagon, and GH responses to iv glucose in normal man. Normal subjects received two consecutive iv glucose tolerance tests (0.33 g/kg) before and after the acute oral administration of 5, or 10 or 20 mg baclofen, respectively, (10 subjects for each group). The dose of baclofen was divided and given 8 and 1 h before the performance of the posttreatment test. A fourth group of normal subjects served as placebo group (8 subjects). The highest dose of baclofen significantly increased insulin responses to glucose and raised basal glucagon levels (P less than 0.01). No significant change occurred with the other doses. Baclofen produced a dose-related increase in basal GH levels; a 10-fold increase was observed with the 20-mg dose. However, glucose-induced glucagon and GH suppression were not affected by baclofen. Despite the increased hormonal secretions, glucose tolerance did not change after baclofen. These results seem to indicate that gamma-aminobutyric acid may play a role in the neuroendocrine control of the pancreatic islets.