Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

Abstract

In healthy humans and rodents, chronic and acute exercise improves subsequent insulin sensitivity of skeletal muscle. A large animal species with similar metabolic responses to exercise would permit longitudinal studies, including repeated biopsies of muscle and other tissues not possible in rodents, and enable study of interactions with insulin-resistant physiological states not feasible in humans. Therefore, we examined whether acute exercise increases insulin sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp (HEC) in mature female sheep (n ϭ 7). Sheep were familiarized to treadmill walking and then performed an acute exercise bout (30 min, 8% slope, up to 4.4 km/h). A second HEC was conducted ϳ18 h after the acute exercise. Musculus semimembranosus biopsies were obtained before and after each HEC. Glucose infusion rate during the HEC increased 40% (P ϭ 0.003) and insulin sensitivity (glucose infusion rate/plasma insulin concentration) increased 32% (P ϭ 0.028) after acute exercise. Activation of proximal insulin signaling in skeletal muscle after the HEC, measured as Ser 473 phosphorylation of Akt, increased approximately five-fold in response to insulin (P Ͻ 0.001) and was unaltered by acute exercise performed 18 h earlier. PGC1␣ and GLUT4 protein, glycogen content and citrate synthase activity in skeletal muscle did not change in response to insulin or exercise. In conclusion, improved insulin sensitivity and unchanged proximal insulin signaling on the day after acute exercise in sheep are consistent with responses in humans and rodents, suggesting that the sheep is an appropriate large-animal model in which to study responses to exercise. exercise; insulin sensitivity; muscle; sheep REGULAR EXERCISE TRAINING increases insulin-stimulated whole body and skeletal muscle glucose uptake in humans, in healthy individuals as well as in those who have Type 2 diabetes (T2D) or are obese or aged (reviewed by Refs. 14, 31, 45). Increased expression of hexokinase 2, some insulin signaling proteins and GLUT4, and greater insulin-induced vasodilation are implicated as mechanisms for enhanced insulin-stimulated glucose uptake after training (14,31,45). Exercise training probably acts mainly at distal sites to increase glucose uptake, with the balance of evidence, suggesting that proximal insulin signaling is not upregulated (14, 38). Importantly, a single bout of exercise also increases the insulin sensitivity of glucose uptake during the following 4 -48 h in healthy humans (34,46,52,54,55). Similar effects have been demonstrated in rodents, where an acute exercise bout increases in vitro insulin-stimulated glucose uptake in mouse muscle 85 min after exercise (18) and in rat muscle collected 3-16 h after a single bout of exercise (8,15,19,43,44). Available evidence from studies in humans and rodents suggests that acute exercise, like exercise training, increases insulin sensitivity without changes in proximal insulin signaling (reviewed in Ref. 31).A large animal model with...

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

“…The ϳ6% impairment in the postexercise enhancement of insulin sensitivity is a small yet statistically significant effect determined via the hyperinsulinemic euglycemic clamp, a technique commonly used as a gold-standard measurement of IS. Although we did not measure resting vs. postexercise IS, it has been shown previously that whole body IS was elevated by 32% 18 h after exercise in sheep (24) and to a similar degree 3 h postexercise in an older overweight population (19). Since exercise is an effective means of improving IS for not only healthy individuals but those with insulin resistance (36), it can be suggested that any impairment to this beneficial effect is clinically relevant.…”

Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by a paternal high‐fat diet

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Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

“…1). Acute exercise can also elevate in vivo insulin-stimulated glucose disposal assessed by the euglycemic hyperinsulinemic clamp in humans (4,79,103,125), rats (81), dogs (87), and sheep (77).…”