Advanced

The functional impact of G protein-coupled receptor 142 (Gpr142) on pancreatic β-cell in rodent

Al-Amily, Israa Mohammad LU ; Dunér, Pontus LU ; Groop, Leif LU and Salehi, Albert LU (2019) In Pflugers Archiv European Journal of Physiology
Abstract

We have recently shown that the G protein-coupled receptor 142 (GPR142) is expressed in both rodent and human pancreatic β-cells. Herein, we investigated the cellular distribution of GPR142 within islets and the effects of selective agonists of GPR142 on glucose-stimulated insulin secretion (GSIS) in the mouse islets and INS-1832/13 cells. Double-immunostaining revealed that GPR142 immunoreactivity in islets mainly occurs in insulin-positive cells. Potentiation of GSIS by GPR142 activation was accompanied by increased cAMP content in INS-1832/13 cells. PKA/Epac inhibition markedly suppressed the effect of GPR142 activation on insulin release. Gpr142 knockdown (Gpr142-KD) in islets was accompanied by elevated... (More)

We have recently shown that the G protein-coupled receptor 142 (GPR142) is expressed in both rodent and human pancreatic β-cells. Herein, we investigated the cellular distribution of GPR142 within islets and the effects of selective agonists of GPR142 on glucose-stimulated insulin secretion (GSIS) in the mouse islets and INS-1832/13 cells. Double-immunostaining revealed that GPR142 immunoreactivity in islets mainly occurs in insulin-positive cells. Potentiation of GSIS by GPR142 activation was accompanied by increased cAMP content in INS-1832/13 cells. PKA/Epac inhibition markedly suppressed the effect of GPR142 activation on insulin release. Gpr142 knockdown (Gpr142-KD) in islets was accompanied by elevated release of MCP-1, IFNγ, and TNFα during culture period and abolished the modulatory effect of GPR142 activation on the GSIS. Gpr142-KD had no effect on Ffar1, Ffar2, or Ffar3 mRNA while reducing Gpr56 and increasing Tlr5 and Tlr7 mRNA expression. Gpr142-KD was associated with an increased expression of Chrebp, Txnip, RhoA, and mitochondrial Vdac1 concomitant with a reduced Pdx1, Pax6, and mitochondrial Vdac2 mRNA levels. Long-term exposure of INS-1832/13 cells to hyperglycemia reduced Gpr142 and Vdac2 while increased Chrebp, Txnip, and Vdac1 mRNA expression. GPR142 agonists or Bt 2 -cAMP counteracted this effect. Glucotoxicity-induced decrease of cell viability in Gpr142-KD INS-1 cells was not affected by GPR142-agonists while Bt 2 -cAMP prevented it. The results show the importance of Gpr142 in the maintenance of pancreatic β-cell function in rodents and that GPR142 agonists potentiate GSIS by an action, which most likely is due to increased cellular generation of second messenger molecule cAMP.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Apoptosis, Cell viability, Confocal image, Type 2 diabetes, β-Cell dysfunction
in
Pflugers Archiv European Journal of Physiology
publisher
Springer
external identifiers
  • scopus:85061623456
ISSN
0031-6768
DOI
10.1007/s00424-019-02262-7
language
English
LU publication?
yes
id
4ca807b1-2a29-454b-b899-ae86b21a13af
date added to LUP
2019-02-26 08:27:57
date last changed
2019-03-27 04:39:22
@article{4ca807b1-2a29-454b-b899-ae86b21a13af,
  abstract     = {<p>                             We have recently shown that the G protein-coupled receptor 142 (GPR142) is expressed in both rodent and human pancreatic β-cells. Herein, we investigated the cellular distribution of GPR142 within islets and the effects of selective agonists of GPR142 on glucose-stimulated insulin secretion (GSIS) in the mouse islets and INS-1832/13 cells. Double-immunostaining revealed that GPR142 immunoreactivity in islets mainly occurs in insulin-positive cells. Potentiation of GSIS by GPR142 activation was accompanied by increased cAMP content in INS-1832/13 cells. PKA/Epac inhibition markedly suppressed the effect of GPR142 activation on insulin release. Gpr142 knockdown (Gpr142-KD) in islets was accompanied by elevated release of MCP-1, IFNγ, and TNFα during culture period and abolished the modulatory effect of GPR142 activation on the GSIS. Gpr142-KD had no effect on Ffar1, Ffar2, or Ffar3 mRNA while reducing Gpr56 and increasing Tlr5 and Tlr7 mRNA expression. Gpr142-KD was associated with an increased expression of Chrebp, Txnip, RhoA, and mitochondrial Vdac1 concomitant with a reduced Pdx1, Pax6, and mitochondrial Vdac2 mRNA levels. Long-term exposure of INS-1832/13 cells to hyperglycemia reduced Gpr142 and Vdac2 while increased Chrebp, Txnip, and Vdac1 mRNA expression. GPR142 agonists or Bt                             <sub>2</sub>                             -cAMP counteracted this effect. Glucotoxicity-induced decrease of cell viability in Gpr142-KD INS-1 cells was not affected by GPR142-agonists while Bt                             <sub>2</sub>                             -cAMP prevented it. The results show the importance of Gpr142 in the maintenance of pancreatic β-cell function in rodents and that GPR142 agonists potentiate GSIS by an action, which most likely is due to increased cellular generation of second messenger molecule cAMP.                         </p>},
  author       = {Al-Amily, Israa Mohammad and Dunér, Pontus and Groop, Leif and Salehi, Albert},
  issn         = {0031-6768},
  keyword      = {Apoptosis,Cell viability,Confocal image,Type 2 diabetes,β-Cell dysfunction},
  language     = {eng},
  month        = {02},
  publisher    = {Springer},
  series       = {Pflugers Archiv European Journal of Physiology},
  title        = {The functional impact of G protein-coupled receptor 142 (Gpr142) on pancreatic β-cell in rodent},
  url          = {http://dx.doi.org/10.1007/s00424-019-02262-7},
  year         = {2019},
}