Defects in Oxygen Supply to Skeletal Muscle of Prediabetic ZDF Rats.
Posted on March 10th, 2010 | by Stem Cell News || Related Articles |
Defects in Oxygen Supply to Skeletal Muscle of Prediabetic ZDF Rats.
Am J Physiol Heart Circ Physiol. 2010 Mar 5;
Authors: Ellis CG, Goldman DG, Hanson MS, Stephenson AH, Milkovich S, Benlamri A, Ellsworth ML, Sprague RS
In humans, prediabetes is characterized by marked increases in plasma insulin and near normal blood glucose levels as well as microvascular dysfunction of unknown origin. Using the extensor digitorum longus (EDL) muscle of 7 week inbred male Zucker diabetic fatty (ZDF) rats fed a high-fat diet as a model of prediabetes, we tested the hypothesis that hyperinsulinemia contributes to impaired O2 delivery in skeletal muscle. Using in vivo video microscopy, we determined that total O2 supply to capillaries in the EDL muscle of prediabetic rats was reduced to 64% of controls with a lower O2 supply rate per capillary and higher O2 extraction resulting in decreased O2 saturation at the venous end of the capillary network. These findings suggest a lower average tissue pO2 in prediabetic animals. In addition, we determined that insulin, at concentrations measured in humans and ZDF rats with prediabetes, inhibited O2-dependent release of ATP from rat RBCs. This inability to release ATP could contribute to impaired O2 delivery observed in rats with prediabetes especially in light of the finding that endothelium-dependent relaxation of resistance arteries from these animals is not different from controls and is not altered by insulin. Computational modeling confirmed a significant 8.3 mmHg decrease in average tissue pO2 as well as an increase in heterogeneity of tissue pO2 implicating a failure of a regulatory system for O2 supply. The finding that insulin attenuates O2-dependent release of ATP from RBCs suggests that this defect in RBC physiology could contribute to a failure in the regulation of O2 supply to meet demand in skeletal muscle in prediabetes. Key words: ATP, erythrocyte, oxygen regulation, microvasculature.
PMID: 20207810 [PubMed - as supplied by publisher]