Effect of high-intensity interval training (HİİT) on dexamethasone-induced insulin resistance and apo J, LRP2 levels in rats

Insulin resistance (IR) is a defining feature of conditions such as obesity, Type 2 Diabetes Mellitus (T2DM), Non alcoholic fatty liver disease (NAFLD), metabolic syndrome, and is also associated with the risk of cardiovascular disease. It impairs the function of skeletal muscles to receive and store glucose and triglycerides, resulting in high blood glucose and triglyceride levels. Sedentary life and unbalanced nutrition play an important role in its emergence. In IR changes in signaling pathways that regulate glucose uptake into skeletal muscle cells cause impaired glucose homeostasis. IR is determined based on the assessment of glucose tolerance and impaired fasting glucose levels. Insulin resistance was reported to occur in 352 million adults worldwide in 2017. Low physical activity decreases insulin sensitivity in muscle tissues and causes adiposity in skeletal muscle and liver. Apolipoprotein J (Apo J) is a protein that has been shown to be involved in numerous physiological processes, including apoptotic cell death, lipid transport, and vascular smooth muscle cell differentiation. The main source of serum Apo J is the liver. It is thought to be involved in glucose homeostasis in the insulin signaling pathway together with low density lipoprotein receptor-related protein 2 (LRP2), one of its identified receptors. The aim of this study was to investigate the effect of high-intensity interval training (HIIT) on skeletal muscle LRP2, serum, and skeletal muscle Apo J levels in rats with insulin resistance with dexamethasone. In the study, 8-week-old Wistar Albino male rats were divided into four groups: Control (n=9), Exercise (n=9), IR (n=9), and IR+Exercise (n=9) ve). The rats in the IR and IR+Exercise groups were administered 1mg/kg/day of dexamethasone for 5 days. The animals in the Exercise and IR+Exercise groups were exercised for 38 minutes a day, five days a week, for 8 weeks, within the framework of the protocol determined by MEC. Insulin resistance homeostasis modal (HOMA-IR), glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), HDL (high-density lipoprotein), LDL (low-density lipoprotein) and triglyceride levels in blood samples taken from all animals by intracardiac method at the end of the exercise program. To determine the effect of HIIT on insulin resistance, total protein, Apo J, LRP2, phosphorylated insulin receptor (pIR), and phosphorylated Akt (pAkt) levels were measured in the Soleus (SOL) and Extensor digitorum longus (EDL) muscles of sacrificed rats after dexamethasone administration. Histological examinations were performed on the SOL and EDL muscles and liver. In our study, glucose and HOMA-IR values were observed higher in the IR group compared to the Control group, while lower in the IR+Exercise group compared to the IR group. Consistently, it was observed that serum insulin values were higher in the IR group compared to the Control group, and lower in the IR+Exercise group compared to the IR group. LRP2 levels were significantly higher in the IR+Exercise group in the SOL muscle and significantly higher in the IR group in the EDL muscle compared to the other groups. Serum and skeletal muscle Apo J levels increased significantly with exercise. No significant changes were observed in skeletal muscle insulin signaling pathway molecules (pIR, pAkt). In histological evaluations, the histological cross-sectional area of the SOL and EDL muscle was observed to be significantly larger in the IR+Exercise group compared to the IR group and significantly smaller in the IR group compared to the Control group. In liver tissues, inflammation and steatosis levels were found to be lower in the IR+Exercise group compared to the IR group. As a result, exercise application caused a reduction in IR and healing effects in the liver and muscle tissue.