title: Olfactory receptor Olfr544 responding to azelaic acid regulates glucagon secretion in α-cells of mouse pancreatic islets.
abstract: Olfactory receptors (ORs) are extensively expressed in olfactory as well as non-olfactory tissues. Although many OR transcripts are expressed in non-olfactory tissues, only a few studies demonstrate the functional role of ORs. Here, we verified that mouse pancreatic α-cells express potential OR-mediated downstream effectors. Moreover, high levels of mRNA for the olfactory receptors Olfr543, Olfr544, Olfr545, and Olfr1349 were expressed in α-cells as assessed using RNA-sequencing, microarray, and quantitative real-time RT-PCR analyses. Treatment with dicarboxylic acids (azelaic acid and sebacic acid) increased intracellular Ca(2+) mobilization in pancreatic α-cells. The azelaic acid-induced Ca(2+) response as well as glucagon secretion was concentration- and time-dependent manner. Olfr544 was expressed in α-cells, and the EC50 value of azelaic acid to Olfr544 was 19.97 μM, whereas Olfr545 did not respond to azelaic acid. Our findings demonstrate that Olfr544 responds to azelaic acid to regulate glucagon secretion through Ca(2+) mobilization in α-cells of the mouse pancreatic islets, suggesting that Olfr544 may be an important therapeutic target for metabolic diseases.
authors: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology DGIST, Daegu 711-873, South Korea.
authors: NaNa
authors: N
authors: Kang
authors: Department of Biotechnology, Konkuk University, Chungju 380-701, South Korea.
authors: Young Yil
authors: YY
authors: Bahk
authors: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology DGIST, Daegu 711-873, South Korea.
authors: NaHye
authors: N
authors: Lee
authors: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology DGIST, Daegu 711-873, South Korea.
authors: YoonGyu
authors: Y
authors: Jae
authors: College of Medicine, Yonsei University, Seoul 120-752, South Korea.
authors: Yoon Hee
authors: YH
authors: Cho
authors: College of Medicine, Yonsei University, Seoul 120-752, South Korea.
authors: Cheol Ryong
authors: CR
authors: Ku
authors: College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 339-700, South Korea.
authors: Youngjoo
authors: Y
authors: Byun
authors: College of Medicine, Yonsei University, Seoul 120-752, South Korea.
authors: Eun Jig
authors: EJ
authors: Lee
authors: Department of Information and Communication Engineering, DGIST, Daegu 711-873, South Korea. Electronic address: mskim@dgist.ac.kr.
authors: Min-Soo
authors: MS
authors: Kim
authors: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology DGIST, Daegu 711-873, South Korea. Electronic address: jkoo001@dgist.ac.kr.
authors: JaeHyung
authors: J
authors: Koo
mesh_terms: D000818:Animals; D002460:Cell Line; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice
chemical_list: D003998:Dicarboxylic Acids; D005934:Glucagon; C010038:azelaic acid
keywords: Azelaic acid; Glucagon; Olfactory receptor; Olfr544; Pancreatic α-cells