PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Endoplasmic reticulum (ER) stress is a key factor in skeletal muscle insulin resistance (IR).
• ER stress induces protein disulfide isomerase family a member 4 (PDIA4) expression, implicated in IR.
• Metformin is known to modulate ER stress-induced IR, but its effect on PDIA4 in skeletal muscle was unclear.

Purpose of the Study:

• To investigate the role of PDIA4 in metformin's effects on skeletal muscle IR.
• To determine if metformin regulates PDIA4 expression in the context of IR.
• To explore PDIA4 as a potential therapeutic target for IR.

Main Methods:

• Utilized palmitate-induced IR in C2C12 cells (in vitro).
• Employed a high-fat diet-induced IR mouse model (in vivo).
• Assessed PDIA4 expression, inflammatory cytokines, and IR markers.

Main Results:

• Palmitate-induced IR increased PDIA4 and inflammatory cytokines in C2C12 cells.
• PDIA4 knockdown reduced IR and inflammation in C2C12 cells.
• Metformin modulated PDIA4 expression and alleviated IR in vitro and in vivo.
• Serum PDIA4 correlated with IR and inflammation in human subjects.

Conclusions:

• PDIA4 is involved in metformin's beneficial effects on skeletal muscle IR.
• PDIA4 plays a role in the pathogenesis of IR and inflammation.
• PDIA4 represents a novel therapeutic target for alleviating skeletal muscle IR.