Effects of Rosemary Extract and Rosemary Extract Polyphenols on Skeletal Muscle Insulin Resistance

Abstract

Skeletal muscle, a major target tissue of insulin, accounts for ~80% of postprandial glucose disposal and plays a significant role in the regulation of glucose homeostasis. Insulin increases muscle glucose uptake by increasing the translocation of intracellularly stored GLUT4 glucose transporters to the plasma membrane through the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway. Impaired PI3K/Akt signaling is associated with skeletal muscle insulin resistance (IR), leading to chronically elevated blood glucose levels followed by a compensatory rise in insulin levels. Rosemary extract increases muscle cell glucose uptake but its effects on high glucose/high insulin-induced insulin resistance are not known and is the focus of the present study. Exposure of L6 myotubes to 25mM glucose and 100nM insulin for 24 h, to mimic hyperglycemia (HG) and hyperinsulinemia (HI), abolished the acute insulin-stimulated glucose uptake (I: 183, HG + HI + I: 112 % of basal), attenuated the insulin-stimulated Akt phosphorylation, while increased IRS-1 Ser636/639 phosphorylation indicating insulin resistance. In addition, HG+HI increased mTOR phosphorylation/activation. Importantly, treatment with RE (5 μg/ml) significantly restored the insulin-stimulated glucose uptake (HG + HI + RE + I: 149% of basal) reduced the HG + HI-induced IRS-1 Ser636/639 phosphorylation and mTOR phosphorylation and increased AMPK phosphorylation. Our data indicate a potential of RE to counteract muscle insulin resistance and more research is required to investigate the mechanisms involved.