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

J Diabetes Investig. 2020 Jul;11(4):814-822. doi: 10.1111/jdi.13214. Epub 2020 Feb 27.

Abstract

Aims/introduction: Taste receptors, T1rs and T2rs, and the taste-selective G-protein, α-gustducin, are expressed outside the taste-sensing system, such as enteroendocrine L cells. Here, we examined whether α-gustducin also affects nutrition sensing and insulin secretion by pancreatic β-cells.

Materials and methods: The expression of α-gustducin and taste receptors was evaluated in β-cell lines, and in rat and mouse islets either by quantitative polymerase chain reaction or fluorescence immunostaining. The effects of α-gustducin knockdown on insulin secretion and on cyclic adenosine monophosphate and intracellular Ca2+ levels in rat INS-1 cells were estimated. Sucralose (taste receptor agonist)-induced insulin secretion was investigated in INS-1 cells with α-gustducin suppression and in islets from mouse disease models.

Results: The expression of Tas1r3 and α-gustducin was confirmed in β-cell lines and pancreatic islets. Basal levels of cyclic adenosine monophosphate, intracellular calcium and insulin secretion were significantly enhanced with α-gustducin knockdown in INS-1 cells. The expression of α-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 α-gustducin knockdown or in mouse islets with decreased expression of α-gustducin.

Conclusions: α-Gustducin is involved in the regulation of cyclic adenosine monophosphate, intracellular calcium levels and insulin secretion in pancreatic β-cells in a manner independent of taste receptor signaling. α-Gustducin might play a novel role in β-cell physiology and the development of type 2 diabetes.

Keywords: Insulin secretion; Taste receptor; α-Gustducin.

MeSH terms

  • Animals
  • Cell Line
  • Cyclic AMP / metabolism
  • Disease Models, Animal
  • Humans
  • Insulin Secretion / physiology*
  • Insulin-Secreting Cells / physiology*
  • Intracellular Calcium-Sensing Proteins / metabolism
  • Islets of Langerhans / physiology*
  • Mice
  • Rats
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / physiology
  • Transducin / metabolism*

Substances

  • Intracellular Calcium-Sensing Proteins
  • Receptors, G-Protein-Coupled
  • taste receptors, type 1
  • taste receptors, type 2
  • gustducin
  • Cyclic AMP
  • Transducin