Maternal exercise improves insulin sensitivity in mature rat offspring

Abstract

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.

Figure 1. Maternal body weight and food intake

(A) Mean running distance per day for female Sprague Dawley rats set up in a breeding scheme. Arrows indicate when male rats were in the cage for breeding and when pups were born. Day 33 corresponds to day of delivery. (B) Voluntary exercise during pregnancy and nursing caused a trend toward decreased dam body weight compared to sedentary control dams at most time points. (C) There were no differences in food intake between sedentary and exercise dams. (D) There were no differences in pup body weights during nursing. Data were aligned for day of delivery in A but not B and C. * P < 0.05 compared to sedentary dams; n = 20 for sedentary and n = 17 for exercise in A – D. Error bars indicate s.e.m.

Figure 2. Female offspring born to exercised dams had improved glucose disposal following a glucose challenge

Fifteen month old female offspring were fasted for 16 hours then given an oral gavage of glucose (2 g/kg body weight). (A) Offspring from exercised dams had significantly decreased fasting insulin compared to offspring from sedentary dams. (B) At 30 and 120 minutes post glucose administration, blood glucose was significantly lower in offspring from exercised dams compared to offspring from sedentary dams. (C) Area under the curve (AUC) of blood glucose levels during the glucose tolerance test was also significantly lower in offspring from exercised dams compared to those from sedentary dams. * P < 0.05 compared to sedentary control; n = 13 for sedentary and n = 10 for exercise in A; n = 16 for sedentary and n = 14 for exercise in B and C. Error bars indicate s.e.m.

Figure 3. Adult female offspring from exercised dams had increased glucose infusion rate during hyperinsulinemic – euglycemic clamp

Female offspring at 17 months of age underwent the hyperinsulinemic – euglycemic clamp procedure to assess whole body insulin sensitivity. Following a 16 hour fast, insulin was infused at a constant rate of 4.0 mU/kg/min for 120 minutes. Glucose was infused simultaneously at varying rates in order to maintain a 120 – 130 mg/dl blood glucose level in the animal. (A) There were no differences in blood glucose levels during the procedure between the two groups. (B) Glucose infusion rate (GIR) needed to maintain target body blood glucose levels was significantly increased in offspring from exercised dams compared to those from sedentary dams. (C) Steady – state GIR (average of the 80 – 120 min GIR) was significantly increased in offspring from exercised dams compared sedentary dams. (D) Plasma insulin levels were significantly lower under basal and clamp conditions in offspring born to exercised dams compared to offspring from sedentary dams. (E) There were no differences in basal condition whole body glucose turnover rates. Under the clamp condition, glucose turnover rate was significantly increased in offspring from exercised dams compared to those from sedentary dams. (F) There were no differences in basal condition hepatic glucose production (HGP). In response to insulin stimulation during the clamp HGP was significantly decreased in offspring from exercised dams compared to offspring from sedentary dams.* P < 0.05 compared to sedentary control; n = 12 for sedentary and n = 9 for exercise in A – F. Error bars indicate s.e.m.

Figure 4. Offspring from exercised dams had increased skeletal muscle glucose uptake during hyperinsulinemic – euglycemic clamp

Following the clamp procedure, tissues were collected to evaluate insulin stimulated 2 – deoxyglucose uptake. Offspring from exercised dams had significantly increased glucose uptake in (A) extensor digitorum longus (EDL) and (B) gastrocnemious (gastroc) muscles compared to offspring from sedentary dams. There were no differences in (C) soleus muscle, (D) visceral (V.) adipose, or (E) subcutaneous (S.) adipose glucose uptake. Offspring from exercised dams had significantly decreased (F) heart glucose uptake compared to those from sedentary dams. * P < 0.05 compared to sedentary control; n = 12 for sedentary and n = 9 for exercise in A – F. Error bars indicate s.e.m.