Glucagon-like peptide-1 potentiates glucose-stimulated insulin secretion via the transient receptor potential melastatin 2 channel.

Abstract:

:The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic β-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1-enhanced insulin secretion, indicating the involvement of TRPM2 in this process. In addition, the results of current recordings of TRPM2 and measurement of the resulting insulin secretion in β-cells in the presence of GLP-1 and various concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2 channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated GLP-1-induced GSIS. By using specific activators or inhibitors, the present study demonstrated that the two primary downstream effectors of the GLP-1 receptor, exchange protein directly activated by cAMP and protein kinase A, differentially influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of the present study provide a novel avenue for the prevention and treatment of diabetes and its complications.

journal_name

Exp Ther Med

authors

Pang B,Kim S,Li D,Ma Z,Sun B,Zhang X,Wu Z,Chen L

doi

10.3892/etm.2017.5136

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

5219-5227

issue

5

eissn

1792-0981

issn

1792-1015

pii

ETM-0-0-5136

journal_volume

14

pub_type

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