Role of autophagy activation in a diabetic rat model with insulin resistance

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance and relative insulin deficiency. An accumulating body of evidence shows that autophagy, a major catabolic pathway involved in degrading and recycling macromolecules and damaged organelles, plays an important role in maintaining the normal β-cell function. Autophagy is involved in the maintenance of β-cell structures like mitochondria and endoplasmic reticulum (ER) which plays important roles in β-cell survival and its impairment is implicated in the pathogenesis of T2DM. The present study aimed to investigate whether autophagy is regulated in T2DM. It also aimed to investigate the effect of autophagy activation “using Rapamycin” or ER stress reduction “using 4-PBA” on diabetic state using a diabetic rat model with insulin resistance. In the present study, for induction of T2DM, Wistar rats were fed a high-fat diet (HFD) for 2 weeks and then injected intraperitoneally with streptozotocin “STZ” (35 mg/kg body weight). One week later, diabetic status of manipulated animals was monitored through measuring blood glucose and insulin levels while insulin resistance was assessed through calculating homeostasis model assessment of insulin resistance (HOMA-IR). Animals whose blood glucose level exceeded 200 mg/dl were considered diabetic and included in the study.