MicroRNA‑106b regulates skeletal muscle insulin sensitivity and glucose homeostasis by targeting mitofusion‑2

Area of Science:

• Metabolism and Endocrinology
• Molecular Biology
• Physiology

Background:

• Skeletal muscle insulin resistance is a key factor in type 2 diabetes.
• MicroRNA-106b (miR-106b) has been linked to insulin resistance, but its specific role in skeletal muscle requires further investigation.
• Understanding the molecular mechanisms underlying insulin resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To investigate the role of miR-106b in skeletal muscle insulin sensitivity and glucose homeostasis in vivo and in vitro.
• To elucidate the molecular targets and pathways regulated by miR-106b in skeletal muscle.
• To determine if miR-106b is a potential therapeutic target for insulin resistance and type 2 diabetes.

Main Methods:

• In vivo studies using mice infected with lentivirus expressing miR-106b or miR-106b sponge.
• In vitro studies using C2C12 myotubes treated with miR-106b mimics, inhibitors, Mfn2 plasmids, or Mfn2 small interfering RNA.
• Assessment of Mitofusion-2 (Mfn2) protein levels, glucose transporter (Glut)4 protein translocation, glucose uptake, fasting blood glucose levels, and glucose tolerance.

Main Results:

• Overexpression of miR-106b in mice led to reduced Mfn2 protein and Glut4 translocation in skeletal muscle, increased fasting blood glucose, and impaired glucose tolerance.
• Inhibition of miR-106b in mice did not significantly alter fasting blood glucose or glucose tolerance.
• In vitro, miR-106b suppressed glucose uptake and Glut4 translocation, effects that were reversed by Mfn2 overexpression or miR-106b inhibition combined with Mfn2 knockdown.

Conclusions:

• MicroRNA-106b directly targets Mfn2, regulating skeletal muscle insulin sensitivity and glucose tolerance.
• Increased miR-106b expression contributes to insulin resistance by downregulating Mfn2 and impairing glucose transport.
• miR-106b represents a potential therapeutic target for managing insulin resistance and type 2 diabetes.