Abstract
Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis
of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used
to treat diabetes.
Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways.
However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet
β cells in
T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet β cell viability and proliferation by MTT and colony formation assays. Western blot
and qRT-PCR were
utilized to examine GPX4 expression in islet β cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet
β cells was investigated by evaluating the
content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to
inhibit ferroptosis of islet β cells was further revealed by the rescue
experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate
cell viability and the proliferative abilities of islet β cells. Moreover, BBR stimulated
GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet β cells, which functioned similarly as ferroptosis inhibitor Fer-1. In
conclusion, BBR suppressed ferroptosis of islet β cells via promoting GPX4 expression, providing new insights into the mechanism of
BBR for islet β cells.
Key words
berberine - GPX4 - type I diabetes mellitus - islet
β cells - ferroptosis
