Insulin Promotes Mitochondrial Respiration and Survival through PI3K/AKT/GSK3 Pathway in Human Embryonic Stem Cells

• DOI: 10.1016/j.stemcr.2020.10.008
• Publication Date: 2020-11-12T16:14:29Z
• Authors: Zhili Ren; Hui Zhong; Chengcheng Song; Chunhao Deng; Hsun-Ting Hsieh; Weiwei Liu; Guokai Chen
• Keywords: Cellular respiration

Insulin is an essential growth factor for the survival and self-renewal of human embryonic stem cells (hESCs). Although it best known as principal hormone promoting glycolysis in somatic cells, insulin's roles hESC energy metabolism remain unclear. In this report, we demonstrate that insulin to sustain mitochondrial respiration rapidly decreased upon removal. Insulin-dependent cell specific, mainly relies on pyruvate glutamine, while glucose suppresses excessive oxidative phosphorylation. Pharmacologic genetic manipulations reveal continuous signal sustains through PI3K/AKT activation downstream GSK3 inhibition. We further show acts inhibition suppress caspase rescue survival. This study uncovers a critical role AKT/GSK3 pathway regulation survival, highlighting accurate assessment hESCs.