Olfactory Receptors Are Expressed in Pancreatic β-cells and Promote Glucose-stimulated Insulin Secretion

Overview

Journal Sci Rep

Specialty Science

Date 2018 Jan 26

PMID 29367680

Citations 23

Authors

Yuichiro Munakata

Tetsuya Yamada

Junta Imai

Kei Takahashi

Sohei Tsukita

Yuta Shirai

Shinjiro Kodama

Yoichiro Asai

Takashi Sugisawa

Yumiko Chiba

Keizo Kaneko

Kenji Uno

Shojiro Sawada

Hiroyasu Hatakeyama

Makoto Kanzaki

Jun-Ichi Miyazaki

Yoshitomo Oka

Hideki Katagiri

Affiliations

Soon will be listed here.

Abstract

Olfactory receptors (ORs) mediate olfactory chemo-sensation in OR neurons. Herein, we have demonstrated that the OR chemo-sensing machinery functions in pancreatic β-cells and modulates insulin secretion. First, we found several OR isoforms, including OLFR15 and OLFR821, to be expressed in pancreatic islets and a β-cell line, MIN6. Immunostaining revealed OLFR15 and OLFR821 to be uniformly expressed in pancreatic β-cells. In addition, mRNAs of Olfr15 and Olfr821 were detected in single MIN6 cells. These results indicate that multiple ORs are simultaneously expressed in individual β-cells. Octanoic acid, which is a medium-chain fatty acid contained in food and reportedly interacts with OLFR15, potentiated glucose-stimulated insulin secretion (GSIS), thereby improving glucose tolerance in vivo. GSIS potentiation by octanoic acid was confirmed in isolated pancreatic islets and MIN6 cells and was blocked by OLFR15 knockdown. While Gα expression was not detectable in β-cells, experiments using inhibitors and siRNA revealed that the pathway dependent on phospholipase C-inositol triphosphate, rather than cAMP-protein kinase A, mediates GSIS potentiation via OLFR15. These findings suggest that the OR system in pancreatic β-cells has a chemo-sensor function allowing recognition of environmental substances obtained from food, and potentiates insulin secretion in a cell-autonomous manner, thereby modulating systemic glucose metabolism.

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