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

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.06.015· OSTI ID:23105696

Leem, Jaechan ^[1]; Shim, Hae-min ^[2]; Cho, Hochan ^[3]; Park, Jae-Hyung ^[2]

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1. Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu, 42472 (Korea, Republic of)
2. Department of Physiology, School of Medicine, Keimyung University, Daegu, 42601 (Korea, Republic of)
3. Division of Endocrinology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, 41931 (Korea, Republic of)

Highlights: • Olfactory receptor Olfr15 is expressed on the plasma membranes of mouse pancreatic β-cells. • Octanoic acid potentiates glucose-stimulated insulin secretion via Olfr15. • Long-term octanoic acid treatment increases the expression of glucokinase via Olfr15. • Olfr15 expression is decreased and octanoic acid-induced insulin secretion is impaired in islets of diabetic model mice. 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 β-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)P{sub 3} receptor (IP{sub 3}R) antagonist also blocked the OA-induced enhancement of GSIS. These results suggest that OA potentiates GSIS via Olfr15 though the PLC-IP{sub 3} 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 IP{sub 3}R antagonist and a Ca{sup 2+}/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 long-term treatment of OA induces GK promoter activity via Olfr15 through the IP{sub 3}-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 β-cells, suggesting that Olfr15 may be an important therapeutic target in type 2 diabetes.

• OSTI ID: 23105696
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
GTP-ASES
INSULIN
MICE
OCTANOIC ACID
PHOSPHOTRANSFERASES