Mechanisms of High Insulin and High Glucose-Induced Skeletal Muscle Insulin Resistance: Focus on Regulation by Adiponectin
Ahlstrom, Penny Felicia Ulrika
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Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, however the cellular processes involved are poorly defined. Autophagy, ER stress, the UPR and oxidative stress are being studied in insulin resistance but the exact role they play and their interrelationships are yet to be established. Adiponectin is a known insulin sensitizer with anti-diabetic properties but there is limited knowledge of the mechanism by which it exerts its insulin sensitizing effect in skeletal muscle. Through several well-established assays I have demonstrated that impaired autophagy caused ER stress and that UPR activation, specifically peIf2, activated autophagy. Adiponectin alleviated ER stress by restoring autophagy, and a correlation between autophagy induction and insulin sensitization by adiponectin was observed. Alleviating oxidative stress with NAC improved insulin sensitivity independent of ER stress and autophagy, and there appeared to be a correlation between downregulating the UPR and improved insulin sensitivity.