The influence of exercise training versus intensive insulin therapy on insulin resistance development in type 1 diabetes.

The etiology of insulin resistance (IR) in Type 1 Diabetes (T1D) is unclear; however, intramyocellular lipids (IMCL) are likely contributors. While exercise lessens IR and IMCL content; T1D patients elevate glycemia to offset exercise-induced hypoglycemic risk. The preferred treatment for T1D patients is tight glucose management through intensive insulin therapy (IIT); however, IIT is accompanied with a sedentary lifestyle. The purpose of this study was to examine IR development and IMCL in combined exercise (DARE; aerobic/resistance) and IIT-treated T1D animals. 76 rats were divided into control sedentary (C), diabetic sedentary (CD), diabetes sedentary intensive insulin therapy (DIT) and DARE groups. Following streptozotocin (STZ), glycemia was maintained at either 9-15 mM (CD, DARE) or 5-9 mM (DIT) using insulin. DARE alternated between running and weighted climbing for 12 weeks. Results demonstrate that DARE exhibited reduced onset of IR compared with C, DIT and CD, indicated by increased glucose infusion rate (hyperinsulinemic-euglycemic-clamp). A shift in lipid metabolism was evident whereby diacylglycerol was elevated in DIT compared to DARE, while triacylglycerol was elevated in DARE. These findings indicate enhanced IMCL metabolism and the sequestration of fat as neutral triacylglycerol leads to reduced IR in DARE. In contrast, IIT and sedentary behavior leads to diacylglycerol accumulation and IR.

Aerobic exercise training improves insulin-induced vasorelaxation in a vessel-specific manner in rats with insulin-treated experimental diabetes.

Vascular insulin resistance often precedes endothelial dysfunction in type 1 diabetes mellitus. Strategies to limit vascular dysfunction include intensive insulin therapy (4-9 mM) and aerobic training. To avoid the risk of hypoglycaemia, individuals often prescribed conventional insulin therapy (9-15 mM) and participate in resistance training. In a model of type 1 diabetes mellitus, this study examined insulin-induced vasomotor function in the aorta and femoral artery to determine (1) whether resistance training with conventional insulin therapy provides the same benefits as aerobic training with conventional insulin therapy, (2) whether aerobic training or resistance training, when paired with conventional insulin therapy, results in superior vasomotor function compared to intensive insulin therapy alone and (3) whether vessel-specific adaptations exist. Groups consisted of conventional insulin therapy, intensive insulin therapy, aerobic training with conventional insulin therapy and resistance training with conventional insulin therapy. Following multiple low doses of streptozotocin, male Sprague-Dawley rats were supplemented with insulin to maintain blood glucose concentrations (9-15 mM: conventional insulin therapy, aerobic training and resistance training; 4-9 mM: intensive insulin therapy) for 12 weeks. Aerobic training performed treadmill exercise and resistance training consisted of weighted climbing. Coinciding with increased Akt signalling, aerobic training resulted in enhanced insulin-induced vasorelaxation in the femoral artery. Intensive insulin therapy displayed increased mitogen-activated protein kinase signalling and no improvement in insulin-stimulated vasorelaxation compared to all other groups. These data suggest that aerobic training may be more beneficial for limiting the pathogenesis of vascular disease in type 1 diabetes mellitus than merely intensive insulin therapy.

Exercise Training Induced Cardioprotection with Moderate Hyperglycemia versus Sedentary Intensive Glycemic Control in Type 1 Diabetic Rats.

Intensive insulin therapy (IIT; 4-7 mmol/L) is the preferred treatment for type 1 diabetes mellitus (T1DM) patients to reduce the risk of cardiovascular disease (CVD). However, this treatment strategy has been questioned as it is accompanied with a sedentary lifestyle leading to weight gain and insulin resistance. T1DM patients who partake in high-intensity aerobic training (AThigh) to reduce CVD often utilize conventional insulin therapy (CIT; 9-15 mmol/L) to offset the risk of hypoglycemia. Moreover, exercise modalities incorporating resistance training (RT) have been shown to further reduce this risk. The purpose of this investigation was twofold: (1) to determine if CIT paired with AThigh results in larger cardioprotection from an ischemia-reperfusion (I-R) injury than IIT and (2) to establish if the integration of RT with AThigh (ART) results in similar cardioprotection as AThigh. Diabetic (D) male Sprague-Dawley rats were divided into D-IIT (n = 12), D-CIT (n = 12), D-AThigh (n = 8), D-RT (n = 8), and D-ART (n = 8). T1DM was induced with streptozotocin, and blood glucose was adjusted with insulin. D-AThigh occurred on a treadmill (27 m/min; 1 hr), D-RT performed weighted ladder climbs, and D-ART alternated daily between AThigh and RT. Exercise occurred 5 days/wk for 12 wks. This investigation demonstrates that cardioprotection following an I-R injury was similar between D-AThigh and D-IIT. This cardioprotection is not exercise-specific, and each provides unique advantages. D-AThigh leads to improved glycemia while insulin sensitivity was enhanced following resistance exercises. Thus, exercise is an effective means to elicit cardioprotection in T1DM. However, in addition to glycemia, other factors should be considered when tailoring an exercise program for T1DM patients.

Effect of Combined Exercise Versus Aerobic-Only Training on Skeletal Muscle Lipid Metabolism in a Rodent Model of Type 1 Diabetes.

OBJECTIVES: Abnormal skeletal muscle lipid metabolism is associated with insulin resistance in people with type 1 diabetes. Although lipid metabolism is restored with aerobic exercise training, the risk for postexercise hypoglycemia is increased with this modality. Integrating resistance and aerobic exercise is associated with reduced hypoglycemic risk; however, the effects of this exercise modality on lipid metabolism and insulin resistance remain unknown. We compared the effects of combined (aerobic + resistance) versus aerobic exercise training on oxidative capacity and muscle lipid metabolism in a rat model of type 1 diabetes. METHODS: Male Sprague-Dawley rats were divided into 4 groups: sedentary control (C), sedentary control + diabetes (CD), diabetes + high-intensity aerobic exercise (DAE) and diabetes + combined aerobic and resistance exercise (DARE). Following diabetes induction (20 mg/kg streptozotocin over five days), DAE rats ran for 12 weeks (5 days/week for 1 hour) on a motorized treadmill (27 m/min at a 6-degree grade), and DARE rats alternated daily between running and incremental weighted ladder climbing. RESULTS: After training, DAE showed reduced muscle CD36 protein content and lipid content compared to CD (p≤0.05). DAE rats also had significantly increased citrate synthase (CS) activity compared to CD (p≤0.05). DARE rats showed reduced CD36 protein content compared to CD and increased CS activity compared to CD and DAE rats (p≤0.05). DARE rats demonstrated increased skeletal muscle lipid staining, elevated lipin-1 protein content and insulin sensitivity (p≤0.05). CONCLUSIONS: Integration of aerobic and resistance exercise may exert a synergistic effect, producing adaptations characteristic of the "athlete's paradox," including increased capacity to store and oxidize lipids.

Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats.

The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.