Myostatin inhibits glucose uptake via suppression of insulin-dependent and -independent signaling pathways in myoblasts

Physiol Rep, 2018 · DOI: 10.14814/phy2.13837 · Published: September 1, 2018

Simple Explanation

This research investigates how myostatin, a protein that inhibits muscle growth, affects glucose uptake in muscle cells. The study found that myostatin reduces the ability of insulin to stimulate glucose uptake. This suggests myostatin contributes to insulin resistance. Myostatin was found to interfere with key signaling pathways that insulin uses to promote glucose uptake, including the IRS-1/PI3K/AKT pathway. It also reduces the amount of Glut4, a protein responsible for transporting glucose into cells. The study also found that myostatin affects another pathway, AMPK, which is important for energy metabolism and glucose uptake. By inhibiting AMPK, myostatin further reduces glucose uptake in muscle cells.

Study Duration

3 days

Participants

C2C12 mouse myoblasts

Evidence Level

Not specified

Key Findings

1
Myostatin significantly reduced basal and insulin-induced IRS-1 tyrosine phosphorylation, expression and activation of PI3K, associated with diminished AKT phosphorylation and elevated GSK3b phosphorylation.
2
Myostatin inhibited Glut4 mRNA and protein expression, and reduced insulin-induced Glut4 membrane translocation and glucose uptake in myoblasts.
3
Myostatin decreased AMP-activated protein kinase (AMPK) activity accompanied by reduced Glut4 gene expression and glucose uptake.

Research Summary

This study investigates the effects of myostatin on insulin action and glucose uptake in C2C12 muscle cells. Myostatin, known for its role in inhibiting muscle growth, is shown to impair insulin-stimulated glucose disposal. The research identifies that myostatin reduces the expression of Glut4 and interferes with insulin signaling pathways (IRS-1/PI3K/AKT). This leads to reduced glucose uptake in muscle cells. The inhibitory effects are Smad2/3 signaling dependent. Myostatin also inhibits AMPK activation, which further contributes to reduced Glut4 expression and glucose uptake. These findings suggest that myostatin induces insulin resistance by affecting both insulin-dependent and independent pathways.

Practical Implications

Targeting Myostatin for Diabetes Treatment

Inhibiting myostatin could improve insulin sensitivity and glucose metabolism in individuals with type 2 diabetes.

Understanding Muscle Atrophy in Diabetes

Myostatin's role in diabetic muscle atrophy could lead to interventions that preserve muscle mass in diabetic patients.

Developing AMPK Activators

Counteracting myostatin's inhibition of AMPK could enhance glucose uptake and energy metabolism in muscle tissue.

Study Limitations

1
The study used C2C12 mouse myoblasts, which may not fully represent human skeletal muscle.
2
The study did not control for potential effects of any suppression of continued differentiation of C2C12 cells by Mstn on insulin signaling.
3
The effects of Mstn on activation of AMPK and expression of PGC1a raise intriguing ques-tions regarding the broader effects of Mstn on cellular energy metabolism.

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