Role of pancreatic thyrotropin releasing hormone in directing insulin secretion to regulatory pathway

Thyrotropin releasing hormone (TRH; pGlu-His-ProNH2) is colocalized in pancreatic β cells in secretory granules with insulin. TRH secretion from pancreatic islets is stimulated by glucose and inhibited by insulin. Disruption of the TRH gene in knockout mice results in hyperglycemia accompanied by impaired insulin secretory response to glucose. To understand role of TRH we blocked the last step of biosynthesis of α−amidated peptides, including TRH by Disulfiram (DS) treatment of adult male rats subcutaneously with 200 mg/kg for five days. TRH in physiological concentration (1 nM) does not affect basal insulin secretion from intact islets. In contrast, basal insulin secretion from islets of DS-treated rats is four times higher compared to controls and could not be stimulated by high-glucose. The addition of 1 nM TRH into medium decreased immediately basal insulin secretion in DS (TRH lacking) islets to control level and normalized also their response to glucose. Absence of the secretory response to glucose in islets from TRH depleted rats is connected with their increase of insulin content. Glucose stimulation together with 1 nM TRH normalized also insulin content in DS islets. Apparently, high insulin content in islets from TRH depleted animals is a result of block of regulatory secretion pathway which is corrected by the addition of TRH. In conclusion, presence of TRH in β cells ensures appropriate low basal (constitutive) insulin secretion and high response to stimulation. Release of TRH induced by glucose has autocrine effect resulting in directing insulin secretion to regulatory pathway

Author(s): Vladimír Štrbák

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