Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor.
A lysophospholipid series, such as lysophosphatidic acid, lysophosphatidylserine, and lysophosphatidylcholine (LPC), is a bioactive lipid mediator with diverse physiological and pathological functions. LPC has been reported to induce insulin secretion from pancreatic beta-cells, however, the precise mechanism has remained elusive to date. Here we show that an orphan G-protein-coupled receptor GPR119 plays a pivotal role in this event. LPC potently enhances insulin secretion in response to high concentrations of glucose in the perfused rat pancreas via stimulation of adenylate cyclase, and dose-dependently induces intracellular cAMP accumulation and insulin secretion in a mouse pancreatic beta-cell line, NIT-1 cells. The Gs-protein-coupled receptor for LPC was identified as GPR119, which is predominantly expressed in the pancreas. GPR119-specific siRNA significantly blocked LPC-induced insulin secretion from NIT-1 cells. Our findings suggest that GPR119, which is a novel endogenous receptor for LPC, is involved in insulin secretion from beta-cells, and is a potential target for anti-diabetic drug development.
Soga
Takatoshi
T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. soga.takatoshi@yamanouchi.co.jp
Ohishi
Takahide
T
Matsui
Tetsuo
T
Saito
Tetsu
T
Matsumoto
Mitsuyuki
M
Takasaki
Jun
J
Matsumoto
Shun-Ichiro
S
Kamohara
Masazumi
M
Hiyama
Hideki
H
Yoshida
Shigeru
S
Momose
Kazuhiro
K
Ueda
Yoshitaka
Y
Matsushime
Hitoshi
H
Kobori
Masato
M
Furuichi
Kiyoshi
K
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D009928:Organ Specificity; D010179:Pancreas; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014018:Tissue Distribution
D006728:Hormones; D007328:Insulin; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled; D005947:Glucose