Exercise does not change the differences in insulin sensitivity inherent to the Genetic Predisposition

Aims: Patients with metabolic syndrome show an increased incidence of heart failure and worse outcome in cardiac surgery. Rats selectively bred for low (LCR) intrinsic aerobic exercise capacity show signs of the metabolic syndrome with reduced systemic insulin sensitivity, compared to their counterparts bred for high intrinsic aerobic capacity (HCR). Exercise has been described to improve insulin sensitivity in patients. However, it remains unclear if exercise is equally effective in genetically different subjects.

Methods: We applied aerobic interval training to male HCR and LCR rats for 4 weeks. We performed echocardiography to assess cardiac function. We studied insulin response in exercised and sedentary HCR and LCR-rats (28 generation, weeks of age average 36 and 41) using the hyperinsulinemic-euglycemic clamp. We assessed changes in systemic glucose infusion and glycolytic rates and also determined glucose uptake in individual organs and tissues in response to insulin.

Results: After 28 generations of selective breeding, LCR displayed a diabetic phenotype (fasting glucose 4.0 ± 0.1 mmol/l vs. 3.5 ± 0.1, p < 0.01) compared to HCR. LCR and HCR differed in their exercise capacity (LCR vs. HCR 194 ± 26 m vs. 1717 ± 37), body weight (523 ± 16 g vs. 379 ± 19) and tibia length (44.0 ± 0.3 mm vs. 41.6 ± 0.4). Echocardiography did not reveal changes in cardiac function or morphology after exercise. Exercise decreased body weight in both LCR and HCR (-17.4% vs. -15.7%) and increased heart to body weight (+12.6% vs. +11.4%). Epididymal fat pads and liver weight were significantly reduced after exercise (fat: -31.7% vs. -51.6%; liver: -18.1% vs. -15.6%). However, other organ weights were not affected. Compared to HCR, LCR displayed higher random glucose, fasting glucose as well as lower glucose infusion rate and glycolysis rate during clamp. These finding was not affected by exercise. In LCR, exercise reduced 2-deoxy glucose uptake in heart (27.7%) and spleen (53.3%). Exercise induced increase in 2-deoxy glucose uptake in gastrocnemius (31.9%) was found in HCR only and was more pronounced in HCR in epididymal fat (29.0% LCR vs. 51.5% HCR).

Conclusion: Genetic predisposition does not affect the impact of exercise on systemic insulin sensitivity. The isolated organ 2-deoxy glucose uptake suggests an increase in insulin sensitivity after exercise with HCR. However these results are based on assessment with a glucose tracer analogue.