Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner.

Kjøbsted R, Treebak JT, Fentz J, Lantier L, Viollet B, Birk JB, Schjerling P, Björnholm M, Zierath JR, Wojtaszewski JF
Diabetes. 2015 64 (6): 2042-55

PMID: 25552597 · DOI:10.2337/db14-1402

An acute bout of exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise, insulin sensitivity to increased glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood but appear to involve an increased cell surface abundance of GLUT4. While increased proximal insulin signaling does not seem to mediate this effect, elevated phosphorylation of TBC1D4, a downstream target of both insulin (Akt) and exercise (AMPK) signaling, appears to play a role. The main purpose of this study was to determine whether AMPK activation increases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type mouse muscle increases insulin sensitivity to stimulate glucose uptake. However, this was not observed in mice with reduced or ablated AMPK activity in skeletal muscle. Furthermore, prior AICAR stimulation enhanced insulin-stimulated phosphorylation of TBC1D4 at Thr(649) and Ser(711) in wild-type muscle only. These phosphorylation events were positively correlated with glucose uptake. Our results provide evidence to support that AMPK activation is sufficient to increase skeletal muscle insulin sensitivity. Moreover, TBC1D4 phosphorylation may facilitate the effect of prior AMPK activation to enhance glucose uptake in response to insulin.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

MeSH Terms (12)

Aminoimidazole Carboxamide AMP-Activated Protein Kinases Animals Biological Transport Blotting, Western Electrophoresis, Polyacrylamide Gel GTPase-Activating Proteins Insulin Mice Muscle, Skeletal Phosphorylation Ribonucleotides

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