AB Purpose: Recent findings have shown that the intrauterine environment can negatively influence long-term insulin sensitivity in the offspring. Here we look at maternal voluntary exercise as an intervention to improve offspring insulin sensitivity and glucose homeostasis. Methods: Female Sprague-Dawley rats were split into sedentary and exercise groups with the exercise cohort having voluntary access to a running wheel in the cage before and during mating, pregnancy, and nursing. Female offspring were weaned into sedentary cages. Glucose tolerance tests and hyperinsulinemic-euglycemic clamp were performed in adult offspring to evaluate glucose regulation and insulin sensitivity. Results: Adult female offspring born to exercised dams had enhanced glucose disposal during glucose tolerance testing (P < 0.05) as well as increased glucose infusion rates (P < 0.01) and whole body glucose turnover rates (P < 0.05) during hyperinsulinemic-euglycemic clamp testing compared with offspring from sedentary dams. Offspring from exercised dams also had decreased insulin levels (P < 0.01) and hepatic glucose production (P < 0.05) during the clamp procedure compared with offspring born to sedentary dams. Offspring from exercised dams had increased glucose uptake in skeletal muscle (P < 0.05) and decreased heart glucose uptake (P < 0.01) compared with offspring from sedentary dams in response to insulin infusion during the clamp procedure. Conclusions: Exercise during pregnancy enhances offspring insulin sensitivity and improves offspring glucose homeostasis. This can decrease offspring susceptibility to insulin-resistant related diseases such as type 2 diabetes mellitus. Maternal exercise could be an easy, short-term, nonpharmacological method of preventing disease in future generations
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