Characterization of the taste receptor‐related G‐protein α‐gustducin in pancreatic β‐cells

AIMS/INTRODUCTION: Taste receptors, T1rs and T2rs, and the taste-selective G-protein, alpha-gustducin, are expressed outside the taste-sensing system, such as enteroendocrine L cells. Here, we examined whether alpha-gustducin also affects nutrition sensing and insulin secretion by pancreatic beta-cells. MATERIALS AND METHODS: The expression of alpha-gustducin and taste receptors was evaluated in beta-cell lines, and in rat and mouse islets either by quantitative polymerase chain reaction or fluorescence immunostaining. The effects of alpha-gustducin knockdown on insulin secretion and on cyclic adenosine monophosphate and intracellular Ca(2+) levels in rat INS-1 cells were estimated. Sucralose (taste receptor agonist)-induced insulin secretion was investigated in INS-1 cells with alpha-gustducin suppression and in islets from mouse disease models. RESULTS: The expression of Tas1r3 and alpha-gustducin was confirmed in beta-cell lines and pancreatic islets. Basal levels of cyclic adenosine monophosphate, intracellular calcium and insulin secretion were significantly enhanced with alpha-gustducin knockdown in INS-1 cells. The expression of alpha-gustducin was decreased in high-fat diet-fed mice and in diabetic db/db mice. Sucralose-induced insulin secretion was not attenuated in INS-1 cells with alpha-gustducin knockdown or in mouse islets with decreased expression of alpha-gustducin. CONCLUSIONS: alpha-Gustducin is involved in the regulation of cyclic adenosine monophosphate, intracellular calcium levels and insulin secretion in pancreatic beta-cells in a manner independent of taste receptor signaling. alpha-Gustducin might play a novel role in beta-cell physiology and the development of type 2 diabetes.