Growth receptor binding protein 10 (Grb10) is an adaptor protein that interacts with the insulin receptor and insulin like growth factor‐1 receptor. Overexpression of Grb10 in muscle cells and adipocytes inhibits insulin signaling and transgenic mice overexpressing Grb10 presented with impaired glucose tolerance. However, the roles of Grb10 in β‐cells remain unknown. Aim of the study was to explore the effect of Grb10 on β‐cell function. Grb10 protein expression was detected in islets or INS 832/13 cells with western blot. The effects of Grb10 on glucose‐stimulated insulin secretion (GSIS) and the insulin/IGF‐1 signaling pathway in islets were investigated in rat islets and/or dispersed islet cells with Grb10 overexpresion by adenovirus transfection. Grb10 is expressed in both human and rat pancreas. Its expression is increased in islets isolated from rats fed with high fat plus high sugar diet compared with those isolated from rats fed with chow diet, and in INS 832/13 cells exposed to high level of glucose (20 mM), palmitate (1 mM), interleukin‐1β (50 U/ml). Overexpression of Grb10 in INS 832/13 cells or rat islets impaired GSIS compared with their respective controls (all P < 0.05). Moreover, the inhibition of GSIS by Grb10 overexpression was associated with decrease of insulin‐ or IGF‐1‐induced Akt and ERK1/2 phosphorylation. Our study demonstrates that Grb10 is an important negative regulator of insulin/IGF‐1 signaling in pancreatic β‐cells and a potential target to improve β‐cell function. This article is protected by copyright. All rights reserved.