• Inhibition of Free fatty acid-Induced Insulin Resistance by Rosemary Extract: Investigation of the Mechanisms Involved

      Filip, Vlavcheski; Applied Health Sciences Program
      Excess of plasma free fatty acids (FFA) are highly associated with insulin resistance and are a major risk factor for the development of type 2 diabetes mellitus. This thesis investigates the effect of rosemary extract and rosemary extract polyphenols carnosic acid (CA), rosmarinic acid (RA) and carnosol (COH) on recovering/blunting FFA-induced insulin resistance in skeletal muscle cells and the mechanism(s) involved. Exposure of L6 myotubes with the FFA palmitate significantly reduced the insulin-stimulated glucose uptake. Most importantly, the insulin-stimulated glucose uptake was restored in the presence of RE and its polyphenols CA, RA and COH. Furthermore, treatment with palmitate increased serine phosphorylation of IRS-1 and significantly decreased the insulin-stimulated phosphorylation of Akt. These effects were completely abolished in the presence of rosemary extract. Additionally, we investigated the effect of palmitate and rosemary extract on the phosphorylation and of JNK, mTOR, P70S6K and AMPK kinases. Our results indicate that palmitate treatment increased the phosphorylation of JNK, mTOR, p70S6K whereas rosemary extract completely abolished this effect. Additionally, rosemary extract increased the phosphorylation of AMPK even in the presence of palmitate. The expression levels of these proteins were not affected by any of the treatments. These results indicate that treatment with rosemary extract attenuated the palmitate-induced phosphorylation of the serine residues of IRS-1, mTOR, p70 S6K and JNK while increasing the phosphorylation of AMPK. Additionally, treatment with RE restored the insulin-stimulated glucose uptake in palmitate-induced insulin resistant cells.
    • Investigating the Biological Effects of Rosemary (Rosmarinus officinalis L.) Extract on Skeletal Muscle Glucose Uptake

      Naimi, Madina; Applied Health Sciences Program (Brock University, 2014-09-10)
      Skeletal muscle (SKM) is the most important tissue in maintaining glucose homeostasis and impairments in this tissue leads to insulin resistance (IR). Activation of 5’ AMP-activated kinase (AMPK) is viewed as a targeted approach to counteract IR. Rosemary extract (RE) has been reported to decrease blood glucose levels but its effects on SKM are not known. We hypothesized that RE acts directly on SKM to increase glucose uptake (GU). We found an increase in GU (184±5.07% of control, p<0.001) in L6 myotubes by RE to levels similar to insulin and metformin. Carnosic acid (CA) and rosmarinic acid (RA), major polyphenols found in RE, increased GU. RE, CA, and RA significantly increased AMPK phosphorylation and their effects on GU was reduced by an AMPK inhibitor. Our study is the first to show a direct effect of RE, CA and RA on SKM GU by a mechanism that involves AMPK activation.