Rotenone protects against β-cell apoptosis and attenuates type 1 diabetes mellitus

Area of Science:

• Biochemistry
• Cell Biology
• Endocrinology

Background:

• Type 1 diabetes mellitus (T1DM) involves pancreatic beta-cell dysfunction and apoptosis, leading to insulin deficiency.
• Defective mitochondrial function is implicated in beta-cell dysfunction and apoptosis in T1DM.
• The specific role of mitochondrial complex I in T1DM pathogenesis requires further elucidation.

Purpose of the Study:

• To investigate the protective effects of mitochondrial complex I inhibition on pancreatic beta cells in a mouse model of T1DM.
• To elucidate the underlying mechanisms of rotenone's protective action in T1DM.

Main Methods:

• Utilized a streptozotocin (STZ)-induced mouse model of T1DM.
• Employed cultured mouse pancreatic beta-cell line (Min6) for in vitro studies.
• Assessed the effects of rotenone (ROT) on glycemic control, insulin levels, inflammation, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential, and mitochondrial biogenesis.

Main Results:

• Rotenone (ROT) treatment demonstrated a hypoglycemic effect and restored insulin levels in STZ-induced T1DM mice.
• ROT significantly decreased pancreatic inflammation and beta-cell apoptosis.
• In vitro, ROT protected beta cells against STZ- and inflammatory cytokine-induced apoptosis, accompanied by reduced ROS and enhanced mitochondrial function.

Conclusions:

• Mitochondrial complex I inhibition, exemplified by rotenone, exhibits protective effects on pancreatic beta cells in T1DM.
• ROT treatment improves mitochondrial function and promotes mitochondrial biogenesis, mediated by PGC-1α.
• Inhibition of mitochondrial complex I represents a promising therapeutic strategy for beta-cell protection in T1DM.