GDF11 does not improve the palmitate induced insulin resistance in C2C12

Eur Rev Med Pharmacol Sci. 2017 Apr;21(8):1795-1802.

Abstract

Objective: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance.

Materials and methods: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro. The mRNA expression of GDF11, GLUT4, IRS-1 (insulin receptor substrate-1) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein level of GDF11 and PGC-1α were detected by Western blot. The glucose uptake was measured by 2NBDG uptake assay.

Results: In high fat diet induced obese mice, both serum level of GDF11 and the expression of GDF11 in skeletal muscle decreased. Similarly, the expression of GDF11 also reduced in palmitate-treated C2C12 myotubes. In vitro, the glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α significantly decreased after palmitate intervention, but GDF11 treatment did not reverse the reduction of glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α in C2C12 myotubes.

Conclusions: We firstly confirmed that the expression of GDF11 decreased both in the skeletal muscle of obese mice and palmitate-treated myotubes, but supplementation GDF11 does not ameliorate the palmitate-induced insulin resistance in C2C12 myotubes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Line
  • Diet, High-Fat
  • Glucose Transporter Type 4 / metabolism
  • Growth Differentiation Factors / metabolism*
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance*
  • Mice
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Obesity / metabolism
  • Palmitates
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Gdf11 protein, mouse
  • Glucose Transporter Type 4
  • Growth Differentiation Factors
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Palmitates
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Slc2a4 protein, mouse