Morphological assessment of pancreatic islet hormone content following aerobic exercise training in rats with poorly controlled Type 1 diabetes mellitus.

Regular exercise has been shown to improve many complications of Type 1 diabetes mellitus (T1DM) including enhanced glucose tolerance and increased cardiac function. While exercise training has been shown to increase insulin content in pancreatic islets of rats with T1DM, experimental models were severely hyperglycemic and not undergoing insulin treatment. Further, research to date has yet to determine how exercise training alters glucagon content in pancreatic islets. The purpose of the present investigation was to determine the impact of a 10-week aerobic training program on pancreatic islet composition in insulin-treated rats with T1DM. Second, it was determined whether the acute, exercise-mediated reduction in blood glucose experienced in rats with T1DM would become larger in magnitude following aerobic exercise training. Diabetes was induced in male Sprague-Dawley rats by multiple low dose injections of streptozotocin (20mg/kg i.p.) and moderate intensity aerobic exercise training was performed on a motorized treadmill for one hour per day for a total of 10 weeks. Rats with T1DM demonstrated significantly less islet insulin, and significantly more islet glucagon hormone content compared with non-T1DM rats, which did not significantly change following aerobic training. The reduction in blood glucose in response to a single exercise bout was similar across 10 weeks of training. Results also support the view that different subpopulations of islets exist, as small islets (<50 µm diameter) had significantly more insulin and glucagon in rats with and without T1DM.

Ischemia-reperfusion injury and hypoglycemia risk in insulin-treated T1DM rats following different modalities of regular exercise.

While regular exercise is known to improve cardiovascular function, individuals with type 1 diabetes mellitus (T1DM) have an increased risk for exercise-induced hypoglycemia. Clinical data suggest that higher intensities of acute exercise may alleviate the onset of hypoglycemia; however, the cardiovascular benefit from these forms of exercise in patients with T1DM has yet to be established. The purpose of this study was to investigate the cardiovascular benefit of different regular exercise regimes, while monitoring blood glucose concentrations during the post-exercise period. Fifty rats (8-week-old Sprague-Dawley male) were equally divided into the following groups: nondiabetic sedentary (C), diabetic sedentary (DS), diabetic low-intensity aerobic exercise (DL), diabetic high-intensity aerobic exercise (DH) or diabetic resistance exercise (DR). Diabetes was induced using multiple streptozotocin injections (5×; 20 mg/kg) while subcutaneous insulin pellets maintained glycemia in a range typical for individuals that exercise with T1DM. Exercise consisted of six weeks of treadmill running (DL and DH) or weighted ladder climbs (DR). The cardiovascular benefit of each exercise program was determined by the myocardial recovery from ischemia-reperfusion injury. Exercise-related cardiovascular protection was dependent on the exercise modality, whereby DH demonstrated the greatest protection following an ischemic-reperfusion injury. Each exercise modality caused a significant decline in blood glucose in the post-exercise period; however, blood glucose levels did not reach hypoglycemic concentrations (<3.0 mmol/L) throughout the exercise intervention. These results suggest that elevating blood glucose concentrations prior to exercise allows patients with T1DM to perform exercise that is beneficial to the myocardium without the accompanying risk of hypoglycemia.

The role of resistance and aerobic exercise training on insulin sensitivity measures in STZ-induced Type 1 diabetic rodents.

UNLABELLED: Individuals with Type 1 Diabetes Mellitus (T1DM) can develop insulin resistance. Regular exercise may improve insulin resistance partially through increased expression of skeletal muscle GLUT4 content. OBJECTIVE: To examine if different exercise training modalities can alter glucose tolerance through changes in skeletal muscle GLUT4 content in T1DM rats. METHODS: Fifty rats were divided into 5 groups; control, diabetic control, diabetic resistance exercised, and diabetic high and low intensity treadmill exercised. Diabetes was induced using multiple low dose Streptozotocin (20 mg/kg/day) injections and blood glucose concentrations were maintained moderately hyperglycemic through subcutaneous insulin pellets. Resistance trained rats climbed a ladder with incremental loads, while treadmill trained rats ran on a treadmill at 27 or 15 m/min, respectively, all for 6 weeks. RESULTS: At weeks 3 and 6, area under the curve measurements following an intravenous glucose tolerance test (AUC-IVGTT) in all diabetic groups were higher than control rats (p<0.05). At 6 weeks, all exercise groups had significantly lower AUC-IVGTT values than diabetic control animals (p<0.05). Treadmill trained rats had the lowest insulin dose requirement of the T1DM rats and the greatest reduction in insulin dosage was evident in high intensity treadmill exercise. Concomitant with improvements in glucose handling improvements, tissue-specific elevations in GLUT4 content were demonstrated in both red and white portions of vastus lateralis and gastrocnemius muscles, suggesting that glucose handling capacity was altered in the skeletal muscle of exercised T1DM rats. CONCLUSIONS: These results suggest that, while all exercise modalities can improve glucose tolerance, each mode leads to differential improvements in insulin requirements and protein content alterations.

High-intensity endurance training results in faster vessel-specific rate of vasorelaxation in type 1 diabetic rats.

This study examined the effects of 6 weeks of moderate- (MD) and high-intensity endurance training (HD) and resistance training (RD) on the vasorelaxation responsiveness of the aorta, iliac, and femoral vessels in type 1 diabetic (D) rats. Vasorelaxation to acetylcholine was modeled as a mono-exponential function. A potential mediator of vasorelaxation, endothelial nitric oxide synthase (e-NOS) was determined by Western blots. Vessel lumen-to-wall ratios were calculated from H&E stains. The vasorelaxation time-constant (τ) (s) was smaller in control (C) (7.2 ± 3.7) compared to D (9.1 ± 4.4) and it was smaller in HD (5.4 ± 1.5) compared to C, D, RD (8.3 ± 3.7) and MD (8.7 ± 3.8) (p<0.05). The rate of vasorelaxation (% · s(-1)) was larger in HD (2.7 ± 1.2) compared to C (2.0 ± 1.2), D (2.0 ± 1.5), RD (2.0 ± 1.0), and MD (2.0 ± 1.2) (p<0.05). τ vasorelaxation was smaller in the femoral (6.9 ± 3.7) and iliac (6.9 ± 4.7) than the aorta (9.0 ± 5.0) (p<0.05). The rate of vasorelaxation was progressively larger from the femoral (3.1 ± 1.4) to the iliac (2.0 ± 0.9) and to the aorta (1.3 ± 0.5) (p<0.05). e-NOS content (% of positive control) was greater in HD (104 ± 90) compared to C (71 ± 64), D (85 ± 65), RD (69 ± 43), and MD (76 ± 44) (p<0.05). e-NOS normalized to lumen-to-wall ratio (% · mm(-1)) was larger in the femoral (11.7 ± 11.1) compared to the aorta (3.2 ± 1.9) (p<0.05). Although vasorelaxation responses were vessel-specific, high-intensity endurance training was the most effective exercise modality in restoring the diabetes-related loss of vascular responsiveness. Changes in the vasoresponsiveness seem to be endothelium-dependent as evidenced by the greater e-NOS content in HD and the greater normalized e-NOS content in the smaller vessels.

Vessel-specific rate of vasorelaxation is slower in diabetic rats.

The rate of adjustment of endothelium-dependent vasorelaxation was examined in the aorta, iliac and femoral arteries of eight control and eight diabetic rats with and without supplementation with vitamin C. Vessels were constricted using 10(-5) M phenylephrine (PE) and relaxed with 10(-4) M acetylcholine (ACh condition) or 10(-4) M ACh plus 10(-4) M vitamin C (ACh + vitamin C condition) in a myography system. Vasorelaxation was modelled as a mono-exponential function using a non-linear regression analysis. The adjustment (τ) of vasorelaxation was faster in control (6.6 ± 3.2 s) compared to diabetic rats (8.4 ± 3.4 s) (p < 0.05). The time-to-steady-state tended to be shorter in control (32.0 ± 13.9 s) compared to diabetic rats (38.0 ± 15.0 s) (p = 0.1). ACh + vitamin C did not speed the vasorelaxation response. The τ for vasorelaxation was shorter in the femoral (6.5 ± 2.7 s) and iliac (6.8 ± 2.5 s) compared to the aorta (9.2 ± 4.2 s) (p < 0.05). The rate of vasorelaxation was greater in the femoral (3.2 ± 1.4%·s(-1)) compared to the iliac (2.0 ± 1.0%·s(-1)) and aorta (1.1 ± 0.4%·s(-1)) in both groups and in the iliac compared to the aorta (p < 0.05) in the control group. In conclusion, the vasorelaxation response was vessel specific with a slower rate of adjustment in diabetic compared to control animals.