Paper of the Month- (March/April 2018) from Dr. Riddell's research group

Dunford EC, Leclair E, Aiken J, Mandel ER, Haas TL, Birot O, Riddell MC. The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats. J Appl Physiol (1985). 2017 Mar 1;122(3):492-502. doi: 10.1152/japplphysiol.00762.2016. Epub 2016 Dec 8.


From the authors:

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease targeting the pancreatic beta-cells causing little to no insulin production, resulting in hyperglycemia. Despite exogenous insulin therapy, individuals with T1D are at an increased risk of long-term microvascular (capillary) and macrovascular complications which can significantly impact their morbidity and mortality. T1D is also associated with impaired capillary growth (angiogenesis) in skeletal muscle. It is generally held that hyperglycemia itself, or some metabolic byproduct of hyperglycemia, induces remodeling of capillaries within the skeletal muscle, resulting in lower capillary-to-fiber ratio (C:F), and ultimately affecting regional overall blood flow. In addition to insulin therapy, regular exercise is an established management strategy for T1D, improving glucose uptake and insulin sensitivity within both the skeletal muscle and adipose tissue. Regular endurance exercise, in healthy individuals, has been shown to increase skeletal muscle capillarization. However, the effects of aerobic training on changes in capillarization in diabetic animals and patients are contradictory.

New capillary growth within the skeletal muscle occurs via existing capillaries through two morphologically different, and separately inducible, forms of physiological angiogenesis termed sprouting or non-sprouting angiogenesis. Exercise training and mechanical loading trigger sprouting angiogenesis, while vasodilation, through α-adrenergic antagonism, promotes non-sprouting angiogenesis. Prazosin, an α1-adrenergic antagonist, has been used in many rodent studies, to selectively increase skeletal muscle C:F, but it has yet to be used as an agent to stimulate capillary growth in an animal model of T1D.

The aim of this study was to evaluate the independent and combined effects of exercise and drug-induced capillary growth (prazosin administration) on vascular complications in a rodent model of T1D.

In this study, T1D rats were exposed to 21 days of either voluntary wheel running exercise, prazosin treatment or the two therapeutic options together. We found that the co-treatment resulted in the most improved capillary growth within both glycolytic and oxidative skeletal muscles of the T1D rats. This co-treatment also resulted in additional improvements in glycemic control and circulating lipid levels, thereby suggesting that the two treatments can act in an additive fashion to improve muscle capillarization and metabolism. These results highlight the importance of exercise on the vascular complications associated with diabetes, and suggest that combining aerobic exercise and prazosin administration, or some form of targeted capillary growth, could lead to a cooperative improvement in peripheral vascular complications linked to T1D and may perhaps prevent future complications through the augmentation of skeletal muscle capillarization and glycemic control.

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