Attenuation of FFA‐induced skeletal muscle insulin resistance by rosemary extract

Abstract

Elevated blood free fatty acids (FFAs), as seen in obesity, impair insulin action in muscle leading to insulin resistance and Type 2 diabetes mellitus. Serine phosphorylation of the insulin receptor substrate (IRS) reduces insulin‐stimulated tyrosine phosphorylation leading to insulin resistance. A number of serine/threonine kinases including JNK, mTOR and p70 6SK have been implicated in serine phosphorylation of IRS‐1 and insulin resistance. Activation of the energy sensor AMP‐activated protein kinase (AMPK) increases glucose uptake and has become an important target to counteract insulin resistance. We reported recently that rosemary extract (RE) increased skeletal muscle cell glucose uptake and activated AMPK. However, its effect on FFA‐induced insulin resistant muscle cells has never been elucidated. In this study, we investigated the effect of RE in palmitate‐induced insulin resistant L6 muscle cells. Glucose uptake was measured using [3H]‐2‐deoxy‐D‐glucose and the signaling molecules involved were investigated by immunoblotting.Exposure of L6 myotubes to the FFA palmitate (P) (0.2 mM, 16 hours) resulted in significant reduction in insulin‐stimulated glucose uptake (I: 201±1.21% and P+I: 117±15.6% of control, P<0.001 respectively) indicating insulin resistance. Importantly, exposure to RE resulted in significant restoration of insulin‐stimulated glucose uptake (179±10.5% of control, P<0.001). Treatment with palmitate increased serine phosphorylation of IRS‐1 and significantly decreased the insulin‐stimulated phosphorylation of Akt and these effects were completely abolished in the presence of RE. Treatment with palmitate increased the phosphorylation/activation of JNK, mTOR and p70 6SK whereas RE completely abolished these effects. RE increased the phosphorylation of AMPK even in the presence of palmitate. Overall, our data indicate that treatment with RE attenuates the FFA‐induced insulin resistance. RE and RE polyphenols may have potent effects against insulin resistance and deserve further study.Support or Funding InformationSupported by a Natural Sciences and Engineering Research Council of Canada (NSERC) grant to ET.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.