Steroidogenic factor 1 protects mice from obesity-induced glucose intolerance via improving glucose-stimulated insulin secretion by beta cells

Yan Guo; Liehua Liu; Yanglei Cheng; Hai Li; Xuesi Wan; Jiajing Ma; Juan Liu; Weiwei Liang; Pengyuan Zhang; Jie Chen; Xiaopei Cao; Hongyu Guan; Haipeng Xiao; Yanbing Li

doi:10.1016/j.isci.2023.106451

Steroidogenic factor 1 protects mice from obesity-induced glucose intolerance via improving glucose-stimulated insulin secretion by beta cells

iScience. 2023 Mar 20;26(4):106451. doi: 10.1016/j.isci.2023.106451. eCollection 2023 Apr 21.

Authors

Yan Guo¹, Liehua Liu¹, Yanglei Cheng¹, Hai Li¹, Xuesi Wan¹, Jiajing Ma¹, Juan Liu¹, Weiwei Liang¹, Pengyuan Zhang¹, Jie Chen¹, Xiaopei Cao¹, Hongyu Guan¹, Haipeng Xiao¹, Yanbing Li¹

Affiliation

¹ Department of Endocrinology and Diabetes Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.

Abstract

As a potential druggable nuclear receptor, steroidogenic factor 1 (SF1) regulates obesity and insulin resistance in the ventromedial hypothalamic nucleus. Herein, we sought to demonstrate its expression and functions in islets in the development of obesity-induced diabetes. SF1 was barely detected in the beta cells of lean mice but highly expressed in those of non-diabetic obese mice, while decreased in diabetic ones. Conditional deletion of SF1 in beta cells predisposed diet-induced obese (DIO) mice to glucose intolerance by perturbing glucose-stimulated insulin secretion (GSIS). Consistently, forced expression of SF1 restored favorable glucose homeostasis in DIO and db/db mice by improving GSIS. In isolated islets and MIN6, overexpression of SF1 also potentiated GSIS, mediated by improvement of mitochondrial ATP production. The underlying mechanisms may involve oxidative phosphorylation and lipid metabolism. Collectively, SF1 in beta cell preserves GSIS to promote beta-cell adaptation to obesity and hence is a potential therapeutic target for obesity-induced diabetes.

Keywords: Cell biology; Human metabolism.