angiogenin and Insulin-Resistance

Tissue cross-talk is emerging as a determinant way to coordinate the different organs implicated in glucose homeostasis. Among the inter-organ communication factors, muscle-secreted myokines can modulate the function and survival of pancreatic beta-cells. Using primary human myotubes from soleus, vastus lateralis and triceps brachii muscles, we report here that the impact of myokines on beta-cells depends on fiber types and their metabolic status. We show that Type I and type II primary myotubes present specific mRNA and myokine signatures as well as a different sensitivity to TNF-alpha induced insulin resistance. Finally, we show that angiogenin and osteoprotegerin are triceps specific myokines with beta-cell protective actions against proinflammatory cytokines. These results suggest that type I and type II muscles could impact insulin secretion and beta-cell mass differentially in type 2 diabetes through specific myokines secretion.

Topics: Cytokines; Diabetes Mellitus, Type 2; Homeostasis; Humans; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Muscle Cells; Muscle Fibers, Skeletal; Muscle, Skeletal; Osteoprotegerin; Primary Cell Culture; Ribonuclease, Pancreatic; Tumor Necrosis Factor-alpha

Adipose tissue produces both vascular growth factors and inhibitors. Since obesity is associated with expansion of the capillary bed in regional adipose depots the balance between these factors may favor angiogenesis.. To investigate the relationship between body mass index and serum concentrations of vascular growth factors in human subjects.. Vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D, soluble VEGF receptor-2 (sVEGFr2), hepatocyte growth factor (HGF), angiopoietin-2, angiogenin and endostatin concentrations were measured in serum collected from 58 lean (24 males, 34 female, mean BMI, 22.2+/-0.3) and 42 overweight and obese (16 males and 26 females, mean BMI, 33.5+/-1.2) subjects after an overnight fast.. Sexual dimorphism was apparent in the serum concentrations of VEGF-C, VEFG-D and angiopoietin-2 with significantly higher levels in female compared to male subject. VEGF, VEGF-C, VEGF-D, soluble VEGF receptor-2, angiopoietin-2, angiogenin and endostatin but not HGF were significantly elevated in overweight and obese subjects. Positive correlations between BMI and the serum concentrations of VEGF-C, VEGF-D, sVEGF-R2, angiopoietin-2, angiogenin and endostatin were observed even after adjustment for gender and age.. Increased levels of vascular growth factors as well as the angiogenesis inhibitor endostatin are present in overweight and obese subjects and may contribute to previously documented increased risk of metastatic disease in obese subjects with cancer.

Topics: Adiponectin; Adult; Analysis of Variance; Angiogenic Proteins; Angiopoietin-2; Endostatins; Female; Hepatocyte Growth Factor; Humans; Insulin Resistance; Leptin; Linear Models; Male; Middle Aged; Obesity; Overweight; Ribonuclease, Pancreatic; Sex Characteristics; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor D; Vascular Endothelial Growth Factor Receptor-2