Insulin resistance is a central mechanism in the pathogenesis of type 2 diabetes mellitus (T2DM), contributing to hyperglycemia and multi-organ dysfunction. This experimental study aimed to investigate the effects of insulin resistance on key insulin-responsive organs, including the pancreas, liver, adipose tissue, and skeletal muscle. Male Wistar rats were assigned to control, high-fat diet (HFD), and T2DM experimental groups. Biochemical parameters such as fasting blood glucose, insulin levels, and HOMA-IR were measured, and tissue samples were analyzed using histological and immunohistochemical methods. The T2DM group exhibited significant hyperglycemia, hyperinsulinemia, and increased HOMA-IR values. Histological analysis revealed pancreatic beta-cell dysfunction, hepatic lipid accumulation and glycogen depletion, adipose tissue hypertrophy with altered adipokine expression, and reduced GLUT4 expression in skeletal muscle. These findings demonstrate the multi-organ impact of insulin resistance and its critical role in the progression of T2DM, highlighting the importance of early interventions targeting insulin sensitivity.

Type 2 diabetes mellitus, insulin resistance, pancreas, liver, adipose tissue, skeletal muscle, HOMA-IR, histology, GLUT4, adipokines.

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