Metformin Perturbs Pancreatic Differentiation from Human Embryonic Stem Cells
figureposted on 2021-05-06, 20:20 authored by Linh Nguyen, Lillian Yuxian Lim, Shirley Suet Lee Ding, Nur Shabrina Amirruddin, Shawn Hoon, Shiao-Yng Chan, Adrian Kee Keong Teo
Metformin is becoming a popular treatment before and during pregnancy but current literature on in utero exposure to metformin lacks long-term clinical trials and mechanistic studies. Current literature on the effects of metformin on mature pancreatic β cells highlighted its dual, opposing, protective or inhibitory, effects depending on metabolic environments. However, the impact of metformin on developing human pancreatic β cells remains unknown. Here, we investigated the potential effects of metformin exposure on human pancreatic β cell development and function in vitro. In the absence of metabolic challenges such as high levels of glucose and fatty acids, metformin exposure impaired the development and function of pancreatic β cells, with downregulation of pancreatic genes and dysfunctional mitochondrial respiration. It also affected the insulin secretion function of pancreatic β cells. These findings call for further in-depth evaluation of the exposure of human embryonic and fetal tissue during pregnancy to metformin, and its implications on long-term offspring health.