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The functional impa...
The functional impact of G protein-coupled receptor 142 (Gpr142) on pancreatic -cell in rodent
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- Al-Amily, Israa Mohammad (författare)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Skåne University Hospital
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- Dunér, Pontus (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - matrix och inflammation i ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Matrix and Inflammation in Atherosclerosis,Lund University Research Groups
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- Groop, Leif (författare)
- University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Salehi, Albert (författare)
- University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2019-02-15
- 2019
- Engelska.
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Ingår i: Pflugers Archiv-European Journal of Physiology. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 471:4, s. 633-645
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- We have recently shown that the G protein-coupled receptor 142 (GPR142) is expressed in both rodent and human pancreatic -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, IFN, and TNF 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 -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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- Type 2 diabetes
- -Cell dysfunction
- Apoptosis
- Cell viability
- Confocal image
- beta-cells
- insulin-secretion
- glucose
- islets
- expression
- dysfunction
- inhibition
- acid
- mice
- Physiology
- β-Cell dysfunction
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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