Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Kinesiology

Supervisor

Dr. J. Kevin Shoemaker

Abstract

Peripheral nerve blood flow (NBF) is critical to nerve health. Impaired NBF control may contribute to the progression of diabetes peripheral neuropathy. The purposes of this dissertation were: i) to investigate the acute and chronic effects of hyperglycemia on basal sciatic NBF (measured via Doppler ultrasound), ii) to examine the potential vasodilatory effects of insulin (euglycemic hyperinsulinemic clamp; 10 mµ•kg-1•min-1) on NBF control in healthy rats and rats with insulin-treated type 1 diabetes (DS) and iii) to determine if exercise training (~75% VO2max, 60 min/day, 5 days/wk for 10 wk) improves vasa nervorum reactivity to insulin and motor nerve conduction velocity (MNCV) in rats with DS. The studies tested the overall hypotheses that i) basal NBF, the vasodilatory response to insulin, and MNCV would be attenuated in rats with DS, and ii) DS-induced deficits would be offset by concurrent exercise training. Rats with DS were hypertensive and featured reduced MNCV (P<0.01). However, DS did not alter: basal NBF; the relationship between NBF and blood pressure; or the vascularization of the sciatic nerve compared to healthy controls (P≥0.50). Based on these data, hypertensive rats with DS may exhibit elevated NBF in the conscious, basal state (P=0.02). Despite similar or possibly elevated basal NBF values compared with control rats, rats with DS displayed impaired insulin-mediated vasodilation (P≤0.01). Deficits in insulin-mediated vasa nervorum dilation and MNCV were prevented by concurrent endurance exercise training in a separate group of rats with DS. Enhanced insulin-mediated vasa nervorum dilation in aerobically exercise trained rats with DS may be explained partially by the observed increase in sciatic nerve endothelial NO synthase expression (P=0.04). The degree of hyperglycemia was similar in both groups with DS, but exogenous insulin requirements were reduced in rats with DS that exercise trained (P=0.02). Perhaps increased insulin sensitivity, and not reduced hyperglycemia, is the mechanism responsible for preserving vasa nervorum and nerve function in exercise-trained rats with DS. Improved insulin signaling in the vasa nervorum may potentiate insulin signaling in the sciatic nerve and protect against diabetic peripheral neuropathy.

Keywords: nerve blood flow, diabetes, hypertension, exercise training, insulin, NO

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