thymosin and Insulin-Resistance

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic diseases linked to metabolic and cardiovascular disorders that impair quality of life and increase morbidity and mortality. There has been significant interest in replacing conventional diagnostic tools such as liver biopsy with non-invasive biomarkers for the diagnosis of NAFLD. Thymosin Beta 4 (Tβ4) is a G-actin sequestering peptide involved in many critical biological processes. This study aimed to evaluate the role of Tβ4 in the diagnosis of NAFLD, and its relation to metabolic syndrome. Eighty patients were enrolled in this study, divided into two equal groups of NAFLD cases (n=40) and a control group (n=40). The two groups were subjected to history taking, physical examination, measurement of waist circumference and body mass index (BMI). Laboratory workup included serum Tβ4, insulin resistance (HOMA-IR), fibrosis-4 score (FIB-4), fatty liver index (FLI) and NAFLD fibrosis score (NFL) were calculated for both groups. Serum Tβ4 was significantly lower in NAFLD patients (P < 0.001) and there was a significant positive correlation between serum Tβ4 and HDL (P = 0.034). On the other hand, there was a significant negative correlation between serum Tβ4 and waist circumference (P < 0.001), total cholesterol level (P < 0.001), insulin level (P < 0.001), HOMA-IR (P < 0.001), serum triglycerides (P= 0.025) and FLI (P = 0.004). Serum Tβ4 at a cut-off value of ≤900 ng/ml had 100 % sensitivity, 100 % specificity, 100% positive predictive value and 100% negative predictive value for the prediction of NAFLD. In conclusion, serum Tβ4 could be used as a biomarker for the diagnosis of NAFLD.

Topics: Biomarkers; Egypt; Fibrosis; Humans; Insulin Resistance; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Quality of Life; Thymosin

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

Prothymosin-α (ProT) is involved in oxidative stress, inflammation, cell proliferation, and apoptosis. Increased oxidative stress and chronic inflammation participate in the pathogenesis of diabetes. A recent study found that ProT is a ligand of toll-like receptor 4, which plays an important role in the development of insulin resistance. However, its physiological role remains poorly understood.. The objective was to investigate whether ProT contributes to the development of insulin resistance.. A total of 185 subjects were recruited and classified into nondiabetes (n = 95) and newly diagnosed diabetes (n = 90) groups. Transgenic mice overexpressing ProT were used to investigate the role of ProT in the development of insulin resistance. Lentiviral vectors carrying short hairpin RNA specific for ProT were delivered via the portal vein to silence hepatic ProT expression in mice with high-fat diet-induced insulin resistance. Glucose uptake was determined in L6 myotubes.. We show that the serum ProT levels of patients with type 2 diabetes were significantly higher than those of normal individuals (mean ± SEM, 419.8 ± 46.47 vs 246.4 ± 27.89 pg/mL; P < .001). Furthermore, ProT transgenic mice exhibited an insulin-resistant phenotype, whereas the silencing of hepatic ProT expression ameliorated high-fat diet-induced insulin resistance in C57BL/6 mice. In vitro studies reveal that ProT induced insulin resistance through a toll-like receptor 4-nuclear factor-κB-dependent pathway.. Our results support the role for ProT in the development of insulin resistance. Therefore, ProT is a potential novel therapeutic target for type 2 diabetes.

Topics: Aged; Animals; Diabetes Mellitus, Type 2; Diet, High-Fat; Gene Silencing; Genetic Vectors; Glucose; Humans; Insulin Resistance; Lentivirus; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Muscle Fibers, Skeletal; NF-kappa B; Protein Precursors; RNA, Small Interfering; Thymosin; Toll-Like Receptor 4

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