Anti-#diabetic action of all-trans #retinoic acid and the orphan G protein coupled receptor GPRC5C in pancreatic β-cells
https://www.jstage.jst.go.jp/article/endocrj/64/3/64EJ16-0338/article
Pancreatic islets express high levels of the orphan G-protein coupled receptor C5C (GPRC5C), the function of which remains to be established. Here we have examined the role of GPRC5C in the regulation of insulin secretion and β-cell survival and proliferation using human and mouse pancreatic islets RNA sequencing in human islets revealed GPRC5C expression correlated with the expression of genes controlling apoptosis, cell survival and proliferation. A reduction in Gprc5c mRNA and protein expression was observed in islets isolated from old mice (>46 weeks of age) compared to that in islets from newborn (<3 weeks) mice Potentiation of glucose-stimulated insulin secretion concomitant with enhanced islet cAMP level by all-trans retinoic acid (ATRA) was attenuated upon Gprc5c-KD.
Our results demonstrate that agents activating GPRC5C represent a novel modality for the treatment and/or prevention of diabetes by restoring and/or maintaining functional β-cell mass.
https://www.jstage.jst.go.jp/article/endocrj/64/3/64EJ16-0338/article
Pancreatic islets express high levels of the orphan G-protein coupled receptor C5C (GPRC5C), the function of which remains to be established. Here we have examined the role of GPRC5C in the regulation of insulin secretion and β-cell survival and proliferation using human and mouse pancreatic islets RNA sequencing in human islets revealed GPRC5C expression correlated with the expression of genes controlling apoptosis, cell survival and proliferation. A reduction in Gprc5c mRNA and protein expression was observed in islets isolated from old mice (>46 weeks of age) compared to that in islets from newborn (<3 weeks) mice Potentiation of glucose-stimulated insulin secretion concomitant with enhanced islet cAMP level by all-trans retinoic acid (ATRA) was attenuated upon Gprc5c-KD.
Our results demonstrate that agents activating GPRC5C represent a novel modality for the treatment and/or prevention of diabetes by restoring and/or maintaining functional β-cell mass.
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#Commensals Suppress Intestinal Epithelial Cell #Retinoic Acid Synthesis to Regulate Interleukin-22 Activity and Prevent Microbial Dysbiosis
https://www.cell.com/immunity/fulltext/S1074-7613(18)30526-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761318305260%3Fshowall%3Dtrue
Retinoic acid (RA), a vitamin A metabolite, regulates transcriptional programs that drive protective or pathogenic immune responses in the intestine, in a manner dependent on RA concentration. Vitamin A is obtained from diet and is metabolized by intestinal epithelial cells (IECs), which operate in intimate association with microbes and immune cells.
Here we found that commensal bacteria belonging to class Clostridia modulate RA concentration in the gut by suppressing the expression of retinol dehydrogenase 7 ( Rdh7) in IECs. Rdh7 expression and associated RA amounts were lower in the intestinal tissue of conventional mice, as compared to germ-free mice. Deletion of Rdh7 in IECs diminished RA signaling in immune cells, reduced the IL-22-dependent antimicrobial response, and enhanced resistance to colonization by Salmonella Typhimurium.
Our findings define a regulatory circuit wherein bacterial regulation of IEC-intrinsic RA synthesis protects microbial communities in the gut from excessive immune activity, achieving a balance that prevents colonization by enteric pathogens
#Commensals Suppress Intestinal Epithelial Cell #Retinoic Acid Synthesis to Regulate Interleukin-22 Activity and Prevent Microbial Dysbiosis
https://www.cell.com/immunity/fulltext/S1074-7613(18)30526-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761318305260%3Fshowall%3Dtrue
Retinoic acid (RA), a vitamin A metabolite, regulates transcriptional programs that drive protective or pathogenic immune responses in the intestine, in a manner dependent on RA concentration. Vitamin A is obtained from diet and is metabolized by intestinal epithelial cells (IECs), which operate in intimate association with microbes and immune cells.
Here we found that commensal bacteria belonging to class Clostridia modulate RA concentration in the gut by suppressing the expression of retinol dehydrogenase 7 ( Rdh7) in IECs. Rdh7 expression and associated RA amounts were lower in the intestinal tissue of conventional mice, as compared to germ-free mice. Deletion of Rdh7 in IECs diminished RA signaling in immune cells, reduced the IL-22-dependent antimicrobial response, and enhanced resistance to colonization by Salmonella Typhimurium.
Our findings define a regulatory circuit wherein bacterial regulation of IEC-intrinsic RA synthesis protects microbial communities in the gut from excessive immune activity, achieving a balance that prevents colonization by enteric pathogens