thymosin-beta(4) and Insulin-Resistance

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in the plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.

Topics: Animals; Case-Control Studies; Cell Line, Tumor; Cell Proliferation; Diabetes Mellitus, Type 2; Disease Models, Animal; Humans; Insulin Resistance; Male; Mice, Inbred C57BL; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Neuronal Outgrowth; Osteoblasts; Physical Endurance; Proteomics; Signal Transduction; Tandem Mass Spectrometry; Thymosin

To evaluate the efficacy of thymosin beta 4 (Tβ(4)) on hyperglycemia and insulin sensitivity in a mouse model of type 2 diabetes mellitus (T2DM).. KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ(4) group, with daily Tβ(4) 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ(4), cholesterol, and triglyceride were measured before and after Tβ(4) treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined.. After Tβ(4) treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ(4) group compared with the KK control group. The KK-Tβ(4) group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ(4) group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ(4) treatment.. Tβ(4) improved glucose intolerance and ameliorated insulin resistance in KK mouse. Tβ(4) may be a potential alternative insulin sensitizer for treatment of T2DM.

Topics: Animals; Blotting, Western; Glucose Tolerance Test; Hyperglycemia; Insulin Resistance; Mice; Thymosin