Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R

被引:23
作者
Pradhan, Geetali [1 ,2 ]
Wu, Chia-Shan [1 ,3 ]
Lee, Jong Han [1 ,4 ]
Kanikarla, Preeti [1 ]
Guo, Shaodong [3 ]
Yechoor, Vijay K. [5 ]
Samson, Susan L. [5 ]
Sun, Yuxiang [1 ,3 ]
机构
[1] Baylor Coll Med, Dept Pediat, USDA ARS Childrens Nutr Res Ctr, Houston, TX 77030 USA
[2] Baylor Coll Med, Interdept Program Translat Biol & Mol Med, Houston, TX 77030 USA
[3] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX 77843 USA
[4] Gachon Univ, Coll Pharm, Incheon 21936, South Korea
[5] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
美国食品与农业研究所;
关键词
GROWTH-HORMONE-SECRETION; PANCREATIC BETA-CELLS; GASTRIC-CANCER CELLS; FOOD-INTAKE; SECRETAGOGUE RECEPTOR; GASTROINTESTINAL-TRACT; MESSENGER-RNA; DELTA CELLS; ISLET-CELL; EXPRESSION;
D O I
10.1038/s41598-017-00888-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin's effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R. We found that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma cells (INS-1) and in pancreatic islets from ghrelin(-/-) mice. Surprisingly, obestatin-induced GSIS was absent in beta-cells in which GHS-R was suppressed. Obestatin-induced insulin secretion was abolished in the circulation of Ghsr(-/-) mice, and in pancreatic islets isolated from Ghsr(-/-) mice. We also found that obestatin-induced GSIS was attenuated in islets isolated from beta-cell-specific Ghsr knockout MIP-Cre/ERT; Ghsr(f/f) mice. Our data collectively demonstrate that obestatin is a potent insulin secretagogue under hyperglycemic condition, and obestatin's effect on insulin secretion is mediated by GHS-R in pancreatic beta-cells. Our findings reveal an intriguing insight that obestatin and ghrelin have opposing effects on insulin secretion, and both are mediated through ghrelin receptor GHS-R.
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页数:10
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