GPR40 activation initiates store-operated Ca²⁺ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells.

ABSTRACT: The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca²⁺ release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca²⁺ release via the IP3 receptor is linked to GIIS potentiation. Recently, stromal interaction molecule (STIM) 1 was identified as a key regulator of store-operated Ca²⁺ entry (SOCE), but little is known about its contribution in GPR40 signaling. We show that GPR40-mediated potentiation of GIIS is abolished by knockdown of IP3 receptor 1 (IP3R1), STIM1 or Ca²⁺-channel Orai1 in insulin-secreting MIN

SUBMITTER: Usui R 

PROVIDER: S-EPMC6820554 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature