“THE ROLE OF OBESITY-RELATED INSULIN RESISTANCE IN MOLECULAR MECHANISMS AND THE DEVELOPMENT OF TYPE 2 DIABETES MELLITUS”

Abstract

Insulin resistance is a complex metabolic disorder characterized by a decreased sensitivity of peripheral tissues—particularly skeletal muscle, liver, and adipose tissue—to insulin action. It is considered a central pathogenic mechanism in the development of type 2 diabetes mellitus (T2DM). Recent scientific studies indicate that insulin resistance is not merely a disorder of carbohydrate metabolism but a key component of the broader metabolic syndrome.

Obesity, especially the accumulation of visceral adipose tissue, is one of the most important predisposing factors for the development of insulin resistance. Adipose tissue is now recognized as an active endocrine organ that secretes various biologically active substances, including adipokines (leptin, adiponectin, resistin) and pro-inflammatory cytokines (TNF-α, IL-6, CRP). The increased production of these mediators leads to a state of chronic low-grade inflammation, which disrupts normal insulin signaling pathways.

At the molecular level, insulin resistance is associated with impairment of key signaling pathways such as IRS-1 (insulin receptor substrate-1), PI3K/Akt, and MAPK, resulting in reduced translocation of GLUT4 transporters to the cell membrane. Consequently, glucose uptake by muscle and adipose cells is impaired, leading to elevated blood glucose levels. This process is initially compensated by hyperinsulinemia; however, over time, it causes functional stress and eventual decompensation of pancreatic β-cells.

The clinical consequences of insulin resistance are not limited to type 2 diabetes mellitus. It also significantly increases the risk of arterial hypertension, dyslipidemia, atherosclerosis, and cardiovascular diseases. Therefore, early detection of insulin resistance and implementation of preventive strategies are considered important tasks of modern endocrinology.

This review article systematically analyzes the pathophysiological mechanisms of obesity-related insulin resistance, its molecular basis, its relationship with metabolic syndrome, and the stages of progression toward type 2 diabetes mellitus based on current scientific literature. In addition, it discusses disruptions in insulin signaling pathways, the role of inflammatory mediators, and modern concepts such as mitochondrial dysfunction. The article also reviews current approaches for early diagnosis and therapeutic strategies aimed at slowing the progression of insulin resistance.