Octanoic acid potentiates glucose-stimulated insulin secretion and expression of glucokinase through the olfactory receptor in pancreatic b-cells

Authors
Jaechan LeemHae-min ShimHochan ChoJae-Hyung Park
Department
Dept. of Internal Medicine (내과학); Dept. of Physiology (생리학)
Issue Date
2018
Citation
Biochemical and Biophysical Research Communications, Vol.503(1) : 278-284, 2018
ISSN
1090-2104
Abstract
Olfactory receptors (ORs) are G protein-coupled receptors that mediate olfactory chemosensation, leading to the perception of smell. ORs are expressed in many tissues, but their functions are largely unknown. Here, we show that the olfactory receptor Olfr15 is highly and selectively expressed in both mouse pancreatic b-cells and MIN6 cells. In addition, octanoic acid (OA), a medium-chain fatty acid, potentiates glucose-stimulated insulin secretion (GSIS). The OA-induced enhancement of GSIS was inhibited by Olfr15 knockdown. Treatment with a PLC inhibitor or an Ins(1,4,5)P3 receptor (IP3R) antagonist also blocked the OA-induced enhancement of GSIS. These results suggest that OA potentiates GSIS via Olfr15 though the PLC-IP3 pathway. Furthermore, long-term treatment with OA increased cellular glucose uptake in MIN6 cells by up-regulating the expression of glucokinase (GK). Moreover, this process was blocked by an IP3R antagonist and a Ca2þ/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor. Similarly, OA stimulated GK promoter activity, while either Olfr15 or CaMKIV knockdown blocked the stimulatory effect of OA on GK promoter activity. These results suggest that longterm treatment of OA induces GK promoter activity via Olfr15 through the IP3-CaMKK/CaMKIV pathway. In islets from type 2 diabetic mice, the expression level of Olfr15 and the OA-induced enhancement of GSIS were strongly reduced. Collectively, our results highlight the crucial role of the olfactory receptor Olfr15 in potentiating GSIS in pancreatic b-cells, suggesting that Olfr15 may be an important therapeutic target in type 2 diabetes.
Keywords
Olfactory receptorOctanoic acidInsulin secretionGlucokinasePancreatic b-cellType 2 diabetes
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/41722
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
Keimyung Author(s)
조호찬; 박재형
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X18313275?via%3Dihub
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