%0 Journal Article
%T Hyperglycaemia correlates with skeletal muscle capillary regression and is associated with alterations in the murine double minute
%A Erin R Mandel
%A Julian Aiken
%A Michael C Riddell
%A Olivier Birot
%J Diabetes and Vascular Disease Research
%@ 1752-8984
%D 2019
%R 10.1177/1479164118805928
%X Type 1 diabetes can have deleterious effects on skeletal muscle and its microvasculature. Our laboratory has recently identified murine double minute-2 as a master regulator of muscle microvasculature by controlling expression levels of two key molecular actors of the angio-adaptive process: the pro-angiogenic vascular endothelial growth factor-A and the anti-angiogenic thrombospondin-1. Here, we show for the first time that in the soleus and plantaris muscles of the diabetes-prone BioBreeding rats, a rodent model of autoimmune type 1 diabetes, murine double minute-2 protein levels are significantly decreased, coinciding with elevated protein levels of thrombospondin-1 and its transcription factor forkhead box O1. Significant capillary regression was observed to similar extent in soleus and plantaris muscles of type 1 diabetic rats. Elevated blood glucose levels were correlated with the loss of capillaries, the reduction in murine double minute-2 expression and with the elevations in thrombospondin-1. Vascular endothelial growth factor-A protein levels were unaltered or even increased in diabetic animals, yet type 1 diabetic animals had less vascular endothelial growth factor receptor-2 abundance. The vascular endothelial growth factor-A/thrombospondin-1 ratio, a good indicator of skeletal muscle angio-adaptive environment, was decreased in type 1 diabetic muscle. Our results suggest that the murine double minute-2¨Cforkhead box O1¨Cthrombospondin-1 pathway plays an important role in angio-regulation of the skeletal muscle in the pathophysiological context of type 1 diabetes
%K Type 1 diabetes
%K skeletal muscle
%K capillaries
%K murine double minute-2
%K thrombospondin-1
%K vascular endothelial growth factor-A
%U https://journals.sagepub.com/doi/full/10.1177/1479164118805928