AICAR reverses ketone body mediated insulin resistance in isolated oxidative muscle

作者：Ivarsson Niklas; Zhang Shi Jin; Katz Abram^*

来源：Biochemical and Biophysical Research Communications, 2011, 414(4): 670-674.

DOI：10.1016/j.bbrc.2011.09.122

• beta-Hydroxybutyrate
• Muscle
• AMPK
• Glucose uptake
• Insulin

Recently it was demonstrated that the ketone body beta-hydroxybutyrate (BOH) inhibits insulin-mediated glucose transport in isolated oxidative muscle, which was associated with decreased phosphorylation of Akt/protein kinase B. The purpose of the present study was to determine if activation of AMP-dependent protein kinase by the pharmacological activator AICAR could reverse the insulin resistance induced by BOH. Isolated mouse soleus muscle was incubated in vitro in the absence or presence of 5 mM BOH for similar to 20 h. Following prolonged incubation, insulin increased 2-deoxyglucose glucose (2-DG) uptake 3-fold, but in the presence of BOH most of the insulin response was lost (only similar to 30% remained). Addition of 2 mM AICAR during the last 2 h of prolonged incubation increased the insulin response in the presence of BOH to similar to 80% of the normal insulin effect on 2-DG uptake. The AICAR-mediated reversal of the insulin resistance was not associated with a restoration of the insulin effect on Akt/protein kinase B phosphorylation. However, AICAR enhanced the insulin-induced phosphorylation of the Akt substrate, AS160. In conclusion, these data demonstrate that AICAR reverses the negative effect of BOH on insulin-mediated glucose uptake and this is attributed to activation of a late step in insulin signaling.

• 出版日期2011-11-4