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. This 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 hyperglycemia of diabetic mice. Inhibition of calcium signaling 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-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 induce Akt/ERK phosphorylation in rodent islets and INS-1E, and these effects were altered in OND and diabetic states. Together, this study indicates that i) GPR120 activation has an insulinotropic influence on β cells with the involvement of calcium signaling; 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.
- Insulin secretion
- Type 2 diabetes mellitus
- ©2016 The Author(s)
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