Abstract
Exercise has a potent insulin-sensitivity enhancing effect on skeletal muscle but the intracellular mechanisms that mediate this effect are not well understood. In muscle, Rac1 regulates both insulin- and contraction-stimulated glucose transport and is dysregulated in insulin resistant muscle. However, whether Rac1 is involved in mediating enhanced insulin sensitivity after an acute bout of exercise is unresolved. To address this question we investigated post exercise whole body (insulin tolerance test) as well as muscle (insulin-stimulated 2DG transport in isolated soleus muscle) insulin sensitivity in inducible muscle-specific Rac1 knockout (mKO) and wildtype littermate (WT) mice. Prior exercise enhanced whole body insulin sensitivity by 40% in WT mice and rescued the insulin intolerance in Rac1 mKO mice by improving whole body insulin sensitivity by 230%. In agreement, prior exercise significantly improved insulin sensitivity by 20% in WT and by 40% in Rac1 mKO soleus muscles. These findings suggest that muscle Rac1 is dispensable for the insulin sensitizing effect of exercise. Moreover, insulin resistance in Rac1 mKO mice can be completely normalized by prior exercise explaining why insulin resistant patients can increase insulin action with exercise despite dysfunctional Rac1 activity in muscle.
Originalsprog | Engelsk |
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Tidsskrift | Endocrinology |
Vol/bind | 157 |
Udgave nummer | 8 |
Sider (fra-til) | 3009-3015 |
Antal sider | 7 |
ISSN | 0013-7227 |
DOI | |
Status | Udgivet - 2016 |