Vladimir Strbak
Slovak Medical University ,Slovakia
Title: Insulin Regulatory Secretory Pathway: Role of Thyrotropin Releasing Hormone
Biography
Biography: Vladimir Strbak
Abstract
Thyrotropin-releasing hormone (TRH) was found in various locations. Pancreatic TRH is colocalized with insulin in the secretory granules of ï¢ cells. High TRH expression in the pancreatic islets in perinatal rat coincides with maturation of the insulin secretory responsiveness to glucose. Prepro-TRH gene disruption in mice results in hyperglycemia, accompanied by impaired insulin response to glucose. We showed that secretion of TRH from islets is stimulated by glucose and inhibited by insulin or somatostatin. These data indicate specific relation between TRH and glucose-induced insulin secretion To induce acute shortage of TRH we blocked the terminal step of the post-translational TRH maturation in adult rat in vivo by disulfiram (DS, 5 day i.p. 200 mg/kg pretreatment) and tested insulin secretion from isolated islets in vitro. TRH in physiological concentration (1 nM) did not affect basal or glucose stimulated insulin secretion. Release of insulin from DS-treated pancreatic islets under basal (unstimulated) conditions was four times higher compared to controls and could not be further stimulated by high-glucose. Addition of 1nM TRH in the incubation medium decreased basal insulin secretion to control levels and normalized response to 16.7 mM glucose of islets from DS treated rats. We conclude that TRH is essential for insulin direction from constitutional to regulatory secretory pathway. This function might be disturbed in diabetes mellitus 2.