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

Publisher: Asian Association for the Study of Diabetes and Blackwell Pub. Asia Country of Publication: Japan NLM ID: 101520702 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2040-1124 (Electronic) Linking ISSN: 20401116 NLM ISO Abbreviation: J Diabetes Investig Subsets: MEDLINE

Original Publication: Tokyo : Asian Association for the Study of Diabetes and Blackwell Pub. Asia

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

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 Ca ²⁺ 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.
(© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

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13418692 Realization of Individually Optimized Medical Treatment for the Diseases Related to Metabolic Syndrome; 21390283 Japan Science and Technology Agency; 16K16614 Japan Science and Technology Agency; 19K09013 Japan Science and Technology Agency; 22S203 National Center for Global Health and Medicine; 27S6001 National Center for Global Health and Medicine; 28S1201 National Center for Global Health and Medicine; 30S1012 National Center for Global Health and Medicine

Keywords: Insulin secretion; Taste receptor; α-Gustducin

0 (Intracellular Calcium-Sensing Proteins)
0 (Receptors, G-Protein-Coupled)
0 (taste receptors, type 1)
0 (taste receptors, type 2)
147979-21-3 (gustducin)
E0399OZS9N (Cyclic AMP)
EC 3.6.5.1 (Transducin)

Date Created: 20200121 Date Completed: 20210706 Latest Revision: 20240329

20240329

PMC7378449

10.1111/jdi.13214

31957256