Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes

Abstract

Context: A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa.

Objective: We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D.

Methods: We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) nondiabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps.

Results: Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (~5%, P = 0.035) and insulin levels (~40%, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (~50%, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (~7%, P = 0.004).

Conclusion: A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.

Fig. 1.

Effect of intensive training on mitochondrial oxidative capacity and insulin sensitivity in eight controls and eight adult offspring of mothers with T2D. Paired data are shown as individual lines, with pre- and posttraining group medians (interquartile ranges) shown as adjacent circles and vertical lines, respectively. A–C, MAPR, for which mitochondria were incubated with glutamate plus malate (GM), succinate plus rotenone (SR), and palmitoyl carnitine plus malate (PCM); D, citrate synthase activity; E, steady-state GIR achieved during a hyperinsulinemic-euglycemic clamp measured between min 300–360; F, fasting insulin concentrations. Mixed-effects analysis of covariance models were used to test the effects of group, time, and their interaction adjusted for baseline values and age. Post hoc analyses were conducted using the Fisher's restricted least significant differences criterion. ww, Wet weight.