Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes

Abstract

Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes

“…Thus EX and improved glycemic status in the absence of EX help treat microvascular dysfunction in patients with T2D, but likely to a different degree, through different mechanisms and differentially in microvascular beds that supply tissues that undergo exercise-induced increases in physiological activity. Evidence we have reviewed here, from humans (20, 23-25, 36, 47, 62, 67, 72, 103, 126, 145) and rodents (11,14,42,55,56,79,86,95,101,102,115), is consistent with the notion that EXinduced adaptations in microvascular structure, as well as vasodilatory and insulin signaling, occur predominantly in the skeletal muscle tissue that undergoes sufficient exercise-induced increases in activity from rest to exercise. Therefore, EX that engages the most skeletal muscle mass and recruits the most muscle fibers within each muscle (i.e., greatest increase in fiber recruitment from rest to exercise), for a sufficient duration, will induce adaptations in the greatest amount of skeletal muscle microvascular tissue.…”

“…These effects may be potentiated by increasing capillary blood flow in previously perfused and underperfused capillaries. Therefore, in patients with insulin resistance or T2D, from a vascular perspective, EX may improve insulin signaling by enhancing microvascular responses to insulin (36,62,95,101,102,115), attenuating microvascular rarefaction (Fig. 4, A-D) (23,67,126) and augmenting capillary blood flow (59,118,119), all of which will augment perfusion and increase glucose and insulin delivery in skeletal muscle (21).…”

The Comparison between Effects of 12 weeks Combined Training and Vitamin D Supplement on Improvement of Sensory-motor Neuropathy in type 2 Diabetic Women

“…This is a guess because of the production of some proteins that are resisting to cellular damages and help to repair the neural damages. [29] In the studies, this protein has been considered as a protector for cells, and it is produced by skeletal muscular contractions that prevent from pain and damage. On the other hand, it has been reported that exercise activities will lead to a reduction of preinflammatory and inflammatory factors.…”

“…[30] Some evidences show that this vitamin will help to increase the trophic factors such as nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), NT3. [2930] A reduction in Vitamin D results looking a reduction in NGF and GDNF and a change in p57 receptor level for neurotrophin (NT). [31] The effects of trophic NGF on dopaminergic neurons and forebrain, and the effects of GDNF on dopaminergic neurons of Basal Ganglia have clearly been shown.…”

“…[1219262931] The explanation is that exercise will enlarge the blood vessels, and this will result in higher blood uptake by the peripheral nerves and, therefore, reduction in numbness and tingling. The recovery of the nerves by the proteins in the blood will result in reduction of pain.…”