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 Pflügers Archiv
471(4).
p.633-645
- 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)
- author
- Al-Amily, Israa Mohammad
LU
; Dunér, Pontus
LU
; Groop, Leif
LU
and Salehi, Albert
LU
- organization
- publishing date
- 2019-02-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Apoptosis, Cell viability, Confocal image, Type 2 diabetes, β-Cell dysfunction
- in
- Pflügers Archiv
- volume
- 471
- issue
- 4
- pages
- 633 - 645
- publisher
- Springer
- external identifiers
-
- scopus:85061623456
- pmid:30767071
- 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
- 2024-04-01 20:53:39
@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}},
keywords = {{Apoptosis; Cell viability; Confocal image; Type 2 diabetes; β-Cell dysfunction}},
language = {{eng}},
month = {{02}},
number = {{4}},
pages = {{633--645}},
publisher = {{Springer}},
series = {{Pflügers Archiv}},
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}},
doi = {{10.1007/s00424-019-02262-7}},
volume = {{471}},
year = {{2019}},
}