posted on 2021-05-06, 20:20authored byLinh 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.