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 gastrointestinal 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 eight controls were investigated. Three tests were performed on three separate days. On day 1, An oral TRH test: a 40 mg TRH tablet, was given. Blood samples for blood glucose (BG), proinsulin (PI), insulin (INS), C-peptide (CP), thyroxine (T₄), triiodothyronine (T₃), and thyrotropin (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 administered 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 pancreatic 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 administration, and afterward, there was only a very slight increase, compared 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 of the inhibitory TRH action on OGTT-induced increase of BG and pancreatic hormone secretion is not clear. It could be due to inhibition of gastric 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 β-cells and that TRH cannot affect the INS processing within the β-cells in these patients.