G-protein-coupled receptor 120 (GPR120) is a putative target for obesity and diabetes therapies. However, it remains controversial whether resident GPR120 plays a direct regulatory role in islet β-cell insulin secretion. The present study examined this issue in isolated rodent islets and rat β-cell line INS-1E, and assessed the role of GPR120 in islet insulin secretion in obese non-diabetic (OND) and diabetic states. GPR120 expression was detected in rodent islet β-cells. Docosahexaenoic acid (DHA) and synthetic GPR120 agonist GSK137647 (GSK) augmented insulin release from rat/mouse islets and INS-1E; DHA effects were partially mediated by GPR40. GPR120 knockdown and overexpression attenuated and enhanced DHA effects in INS-1E respectively. DHA and GSK improved postprandial hyperglycaemia of diabetic mice. Inhibition of calcium signalling in INS-1E reduced GPR120 activation-induced insulinotropic effects. The insulinotropic effects of DHA/GSK were amplified in OND rat islets, but diminished in diabetic rat islets. GPR120 and peroxisome proliferator-activated receptor γ (PPARγ) expression were elevated in OND islets and palmitic acid (PA)-treated INS-1E, but reduced in diabetic islets and high glucose-treated INS-1E. PPARγ activation increased GPR120 expression in rat islets and INS-1E. DHA and GSK induced protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) phosphorylation in rodent islets and INS-1E, and these effects were altered in OND and diabetic states. Taken together, the present study indicates that (i) GPR120 activation has an insulinotropic influence on β-cells with the involvement of calcium signalling; (ii) GPR120 expression in β-cells and GPR120-mediated insulinotropic effects are altered in OND and diabetic states in distinct ways, and these alterations may be mediated by PPARγ.
Skip Nav Destination
Article navigation
February 2017
-
Cover Image
Cover Image
Density-dependent scanning electron microscopy of calcifying vascular tissue (orange - calcification; green - collagen). Please see pp. 181-195 for more information. Image provided by Sergio Bertazzo.
Research Article|
January 18 2017
Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states
Dan Zhang;
Dan Zhang
*School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Search for other works by this author on:
Wing Yan So;
Wing Yan So
*School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Search for other works by this author on:
Yi Wang;
Yi Wang
*School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Search for other works by this author on:
Shang Ying Wu;
Shang Ying Wu
*School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Search for other works by this author on:
Qianni Cheng;
Qianni Cheng
*School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Search for other works by this author on:
Po Sing Leung
*School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Correspondence: Po Sing Leung (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 20 2016
Revision Received:
December 13 2016
Accepted:
December 15 2016
Accepted Manuscript online:
December 15 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (3): 247–260.
Article history
Received:
July 20 2016
Revision Received:
December 13 2016
Accepted:
December 15 2016
Accepted Manuscript online:
December 15 2016
Citation
Dan Zhang, Wing Yan So, Yi Wang, Shang Ying Wu, Qianni Cheng, Po Sing Leung; Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states. Clin Sci (Lond) 1 February 2017; 131 (3): 247–260. doi: https://doi.org/10.1042/CS20160545
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |