Glucose stimulates and insulin inhibits release of pancreatic TRH in vitro

Abstract

Objective: Pancreatic TRH is present in insulin-producing B-cells of the islets of Langerhans. There is fragmentary evidence that it may be involved in glucoregulation. The aim of our present study was to analyze how glucose and insulin affect TRH secretion by the pancreatic islets. Design: Isolated pancreatic islets were incubated with different concentrations of glucose, insulin and glucagon, and TRH release was measured.Results: In the present study, 6 and 12 mmol/l D-glucose caused significant TRH release from isolated adult rat pancreatic islets when compared with that in the presence of the same concentrations of biologically ineffective L-glucose. Thirty mmol/l D-glucose was also ineffective, but this was not due to depression of secretion by hyperosmolarity since isosmotic compensation for the high glucose addition did not restore its stimulatory effect. Five mmol/l dibutyryl cyclic 3 0 ,5 0 -adenosine monophosphate (db-cAMP) increased both basal and glucose-stimulated TRH release, but this effect was not seen with 50 mmol/l db-cAMP. Stimulation of phosphodiesterase by imidazole resulted in decreased basal but not glucose-stimulated release of TRH. Glucagon (10 ¹7 mol/l) did not affect either basal or glucosestimulated release of TRH, while insulin (10 ¹7 and 10 ¹6 mol/l) inhibited both. Conclusion: Our present data showing that glucose stimulates and insulin inhibits pancreatic TRH release are compatible with the possibility that this substance may play a role in glucoregulation.

Different Signaling Pathways Involved in Glucose- and Cell Swelling-Induced Insulin Secretion by Rat Pancreatic Islets <i>in Vitro</i>

“…Secretion induced by extracellular hyposmolarity is due to the relative reduction of extracellular compared to intracellular osmolarity and not to dilution of any essential extracellular elements. If medium dilution is made with aqueous 5% mannitol to maintain isosmolarity on both sides of the plasma membrane [30], or by biologically inactive L-glucose [16,31], no secretion is induced. Similarly the insulin response did not occur if the reduction in NaCl was compensated by the addition of an equivalent osmolar amount of sorbitol or choline chloride [2,6].…”

Cell Volume Induced Hormone Secretion: Studies on Signal Transduction and Specificity

“…TRH released into the medium was determined directly by specific radioimmunoassay [17]. The antibody, prepared in our laboratory, is highly specific for TRH and does not exhibit significant cross-reactivity (<0.1%) with pGlu-Glu-Pro-NH 2 , TRH free acid, His-Pro diketopiperazine, TRH-Gly or Lys-Arg-GluHis-Pro-Gly.…”

A role of thyrotropin-releasing hormone in insulin secretion by isolated rat pancreatic islets

“…TRH is colocalized with insulin in the b cells of the pancreatic Langerhans islets and at least during the neonatal period, even in the same secretory granules as insulin (Leduque et al 1989), thus rising possibility of its autocrine regulation [1,18]. TRH secretion from isolated pancreatic islets was stimulated by high concentrations of glucose, whereas insulin added in vitro inhibited glucose-induced TRH release in our previous study [4]. On the other hand, TRH in pharmacological concentrations increased glucose-induced insulin secretion from clonal cells and from perifused pancreatic islets [15].…”

“…At the end of each incubation period, the medium was harvested for insulin levels, which were measured by insulin radioimmunoassay [(RIA) see method below]. The insulin content was also determined in pancreatic islets after their sonication in 1 ml 1 M acetic acid and subsequent extraction as previously described elsewhere [4].…”