Pancreatic β cells compensate with intense insulin secretion in obese individuals, failure of which marks a vital step in progression to type 2 diabetes (T2DM) . Steroidogenic factor-1 (SF-1) is a nuclear receptor which also locates in non-steroidogenic tissues and participates in metabolic regulation. Through immunofluorescence conducted on the pancreas of obese mice, we detected SF1 in the β cells which was surprisingly absent in that of diabetic mice. Genetic deletion of SF1 in β cells predisposed mice to glucose intolerance upon high fat diet (HFD) by perturbing glucose-stimulated insulin secretion (GSIS) , while its ectopic expression by adeno-associated virus (AAV) improved GSIS. Furthermore, we illustrated that mitochondrial improvement may be the underlying mechanism via experiments such as oxygen consumption rate (OCR) , calcium detection and bioinformatics.
In conclusion, SF1 played an important role in β-cell adaptation to lipotoxicity in the obese individuals, which supported SF1 as a potential target for T2DM treatment.
Y.Guo: None. L.Liu: None. Y.Li: None.
This work was supported by National Key Research and Development Program of China (no. 2018YFC1314100) awarded to L.-Y.B.; National Natural Science Foundation of China (no. 81870557) awarded to L.-Y.B.; Key Field Research and Development Program of Guangdong Province, China (no. 2019B020230001) awarded to L.-Y.B.; Natural Science Foundation of Guangdong Province (no. 2016A030313239 and 2014A030313018) awarded to W.-X.S.; Guangdong Basic and Applied Basic Research Foundation (no. 2020A1515010049) awarded to L.H.; and Graduate Innovative Development Program (no. 19ykyjs08) awarded to G.Y