Plasma and Muscle Myostatin in Relation to Type 2 Diabetes

Objective Myostatin is a secreted growth factor expressed in skeletal muscle tissue, which negatively regulates skeletal muscle mass. Recent animal studies suggest a role for myostatin in insulin resistance. We evaluated the possible metabolic role of myostatin in patients with type 2 diabetes and healthy controls. Design 76 patients with type 2 diabetes and 92 control subjects were included in the study. They were matched for age, gender and BMI. Plasma samples and biopsies from the vastus lateralis muscle were obtained to assess plasma myostatin and expression of myostatin in skeletal muscle. Results Patients with type 2 diabetes had higher fasting glucose (8.9 versus 5.1 mmol/L, P<0.001), plasma insulin (68.2 versus 47.2 pmol/L, P<0.002) and HOMA2-IR (1.6 versus 0.9, P<0.0001) when compared to controls. Patients with type 2 diabetes had 1.4 (P<0.01) higher levels of muscle myostatin mRNA content than the control subjects. Plasma myostatin concentrations did not differ between patients with type 2 diabetes and controls. In healthy controls, muscle myostatin mRNA correlated with HOMA2-IR (r = 0.30, P<0.01), plasma IL-6 (r = 0.34, P<0.05) and VO2 max (r = −0.26, P<0.05), however, no correlations were observed in patients with type 2 diabetes. Conclusions This study supports the idea that myostatin may have a negative effect on metabolism. However, the metabolic effect of myostatin appears to be overruled by other factors in patients with type 2 diabetes.

[1]  T. Hornberger,et al.  Faculty Opinions recommendation of Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. , 2014 .

[2]  P. Gluckman,et al.  Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway , 2011, Diabetologia.

[3]  Dahai Zhu,et al.  Myostatin regulates glucose metabolism via the AMP-activated protein kinase pathway in skeletal muscle cells. , 2010, The international journal of biochemistry & cell biology.

[4]  M. Kuhn,et al.  Postnatal PPARδ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice , 2010, PloS one.

[5]  G. Frühbeck,et al.  Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice , 2009, PloS one.

[6]  A. Vaag,et al.  Gene Expression in Skeletal Muscle Biopsies from People with Type 2 Diabetes and Relatives: Differential Regulation of Insulin Signaling Pathways , 2009, PloS one.

[7]  A. Dorner,et al.  Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration , 2009, Molecular and Cellular Endocrinology.

[8]  O. Gavrilova,et al.  Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity , 2009, PloS one.

[9]  N. Gekakis,et al.  Loss-of-Function Mutation in Myostatin Reduces Tumor Necrosis Factor α Production and Protects Liver Against Obesity-Induced Insulin Resistance , 2009, Diabetes.

[10]  D. Hittel,et al.  Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women , 2009, Diabetes.

[11]  J. Gehl,et al.  Association between interleukin-15 and obesity: interleukin-15 as a potential regulator of fat mass. , 2008, The Journal of clinical endocrinology and metabolism.

[12]  D. Allen,et al.  Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. , 2008, American journal of physiology. Endocrinology and metabolism.

[13]  P. Costelli,et al.  Muscle wasting in diabetic and in tumor-bearing rats: role of oxidative stress. , 2008, Free radical biology & medicine.

[14]  B. D. Rodgers,et al.  Clinical, agricultural, and evolutionary biology of myostatin: a comparative review. , 2008, Endocrine reviews.

[15]  M. Mitchell,et al.  Myostatin regulates glucose uptake in BeWo cells. , 2007, American journal of physiology. Endocrinology and metabolism.

[16]  S. Trappe,et al.  Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle. , 2007, Journal of applied physiology.

[17]  B. Pedersen,et al.  Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes , 2007, Diabetologia.

[18]  Robert V Farese,et al.  Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects , 2006, Proceedings of the National Academy of Sciences.

[19]  A. Shield,et al.  Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes. , 2006, American journal of physiology. Endocrinology and metabolism.

[20]  M. Mitchell,et al.  Myostatin is a human placental product that regulates glucose uptake. , 2006, The Journal of clinical endocrinology and metabolism.

[21]  J. Morley,et al.  Cachexia: pathophysiology and clinical relevance. , 2006, The American journal of clinical nutrition.

[22]  R. Wall,et al.  Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance. , 2005, Biochemical and biophysical research communications.

[23]  Karim Bouzakri,et al.  Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. , 2005, Diabetes.

[24]  J. Cross,et al.  Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women. , 2005, American journal of physiology. Endocrinology and metabolism.

[25]  B. Saltin,et al.  Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. , 2004, American journal of physiology. Endocrinology and metabolism.

[26]  Heather Smith,et al.  Resistance training alters plasma myostatin but not IGF-1 in healthy men. , 2004, Medicine and science in sports and exercise.

[27]  E. Metter,et al.  Myostatin Gene Expression is Reduced in Humans with Heavy-Resistance Strength Training: A Brief Communication , 2003, Experimental biology and medicine.

[28]  S. Arver,et al.  Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Levy,et al.  Correct Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program , 1998, Diabetes Care.

[30]  P. Åstrand,et al.  A nomogram for calculation of aerobic capacity (physical fitness) from pulse rate during sub-maximal work. , 1954, Journal of applied physiology.

[31]  C. Fischer Interleukin-6 in acute exercise and training: what is the biological relevance? , 2006, Exercise immunology review.