Adipose Tissue from Subjects with Type 2 Diabetes Exhibits Impaired Capillary Formation in Response to GROα: Involvement of MMPs-2 and -9

Type 2 Diabetes (T2D) is associated with impaired vascularization of adipose tissue (AT) and skeletal muscle. IL8, GROα and IL15 are pro-angiogenic myokines; T2D myotubes secrete high levels of all 3 factors. We aimed to explore the direct impact of these myokines on AT vascularization. Subcutaneous AT explants from subjects with T2D (n=15) and without diabetes (non-diabetic, ND, n=14) subjects were treated with rIL8, rGROα and rIL15 in concentrations equal to those in conditioned media (CM) from T2D and ND myotubes, and sprout formation evaluated. Endothelial cells (EC) were isolated from T2D and ND-AT, treated with rGROα and tube formation evaluated. Finally, we investigated the involvement of MMP-2 and -9 in AT vascularization. ND and T2D concentrations of IL8 or IL15 individually or as IL8 + IL15 + GROα caused similar stimulation of sprout formation in ND- and T2D-AT. GROα alone exerted a similar effect in ND-AT. However, when T2D-AT explants were exposed to GROα alone, sprout formation in response to T2D concentrations was reduced compared to ND (p<0.05). Endothelial-cells (EC) isolated from T2D and ND-AT and treated with GROα exhibited a similar response to that of AT. Exposure of EC from T2D-AT to GROα at T2D concentrations resulted in reduced tube formation compared to ND-AT (p<0.005). Reduced responses to GROα in T2D-AT and EC were also seen for secretion of MMP-2 and -9. The data indicate that skeletal muscle can potentially regulate AT vascularization, with T2D-AT having impairments in sensitivity to GROα and secretion of MMP-2 and -9, while responding normally to IL8 and IL15.