INHIBITORY-ACTION OF ORAL THYROTROPIN-RELEASING-HORMONE ON THE GLUCOREGULATORY RESPONSE OF THE ORAL GLUCOSE-TOLERANCE TEST

Thyrotropin-releasing hormone (TRH) has been found in the gastrointest inal tract, where it mainly exerts an inhibitory action. We used oral TRH, a stable and powerful formulation, to explore the glucoregulatory response of oral glucose tolerance test (OGTT) on obese patients with impaired glucose tolerance (IGT). Seven obese patients with IGT and e ight controls were investigated. Three tests were performed on three s eparate days. On day 1, An oral TRH test: a 40 mg TRH tablet, was give n. Blood samples for blood glucose (BG), proinsulin (PI), insulin (INS ), C-peptide (CP), thyroxine (T-4), triiodothyronine (T-3), and thyrot ropin (TSH) were collected every 30 minutes for 3 hours. On day 2, an OGTT with 75 g glucose was performed. On day 3, an oral TRH test was a dministered 30 minutes before the OGTT, and blood was collected every 30 minutes for 3 hours. Oral-TRH had no effect on basal BG and on panc reatic hormone secretion. Oral TRH, coupled with OGTT in both controls and obese patients, led to a significant inhibition of BG (p < 0.01), of CP (p < 0.001), and of INS (p < 0.001) during the first hour of ad ministration, and afterward, there was only a very slight increase, co mpared with levels after only OGTT treatment. After OGTT, PI peaked at 90 minutes (9.4 +/- 3 ng/mL) in controls and at 60 minutes (12.7 +/- 2.5 ng/mL) in obese patients. TRH application prior to OGTT inhibited PI secretion for 90 minutes in controls, whereas in obese patients PI levels were decreased, not inhibited, during the OGTT. The mechanism o f the inhibitory TRH action on OGTT-induced increase of BG and pancrea tic hormone secretion is not clear. It could be due to inhibition of g astric motility, and on a paracrine effect that enhances secretion of somatostatin that then suppresses INS, CP, and possibly PI levels. The partial escape of PI from the TRH blockade in obese patients with IGT might indicate a diminished functioning capability of beta-cells and that TRH cannot affect the INS processing within the beta-cells in the se patients.