METABOLIK KASALLIKLARDA INSULINREZISTENTLIK RIVOJLANISHINING MOLEKULYAR VA PATOGENETIK MEXANIZMLARI.

KIRISH: insulinrezistentlik 2-tip qandli diabet, semizlik, metabolik disfunksiya bilan bog‘liq steatotik jigar kasalligi (MASLD), arterial gipertenziya, dislipidemiya va polikistik tuxumdon sindromi kabi holatlarning patogenezida muhim o‘rin tutadi. ADA 2026 ma’lumotlariga ko‘ra, og‘ir semizlik, jismoniy faollikning pastligi, MASLD va polikistik tuxumdon sindromi insulinrezistentlik bilan bog‘liq klinik holatlar qatoriga kiradi. MAQSAD: zamonaviy ilmiy adabiyotlar tahlili asosida insulinrezistentlikning kelib chiqish mexanizmlari, molekulyar patogenezi, ektopik lipid metabolitlarining roli va mitoxondrial disfunksiyaning o‘zaro bog‘liqligini o‘rganishdir. MATERIALLAR VA METODLAR: tadqiqotda glyukoza–yog‘ kislotalari sikli, erkin yog‘ kislotalari bo‘yicha fundamental ilmiy ishlar, giperinsulinemik-evglikemik klemp usullari va magnit-rezonans spektroskopiya natijalari qiyosiy umumlashtirildi. HUHOKAMA VA NATIJALARL: energiya ortiqchaligi sharoitida jigar va skelet mushaklarida DAG va seramidlar to‘planib, insulin signalizatsiyasini buzadi. Shuningdek, adipoz to‘qimaning endokrin faolligi kuchayib, metabolik yallig‘lanishni keltirib chiqarishi isbotlandi. XULOSA: insulinrezistentlik ko‘p omilli patofiziologik qayta qurilish bo‘lib, kelgusida ektopik lipid fraksiyalari, mitoxondrial disfunksiyaning birlamchi/ikkilamchi tabiati va genetik-epigenetik omillarni o‘rganish dolzarb vazifa bo‘lib qolmoqda.

INTRODUCTION: insulin resistance plays an important role in the pathogenesis of type 2 diabetes mellitus, obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), arterial hypertension, dyslipidemia, and polycystic ovary syndrome. According to the American Diabetes Association (ADA) 2026 data, severe obesity, low physical activity, MASLD, and polycystic ovary syndrome are among the clinical conditions associated with insulin resistance. AIM: the objective of this study is to systematically examine the mechanisms of origin, molecular pathogenesis, the role of ectopic lipid metabolites, and the interconnection of mitochondrial dysfunction in insulin resistance based on an analysis of modern scientific literature. MATERIALS AND METHODS: the study comparatively generalized the glucose–fatty acid cycle, fundamental scientific works on free fatty acids, hyperinsulinemiceuglycemic clamp methods, and magnetic resonance spectroscopy results. DISCUSSION AND RESULTS: under conditions of energy excess, DAG and ceramides accumulate in the liver and skeletal muscle, impairing insulin signaling. Furthermore, it was proven that enhanced endocrine activity of adipose tissue induces metabolic inflammation. CONCLUSION: Insulin resistance is a multifactorial pathophysiological remodeling, and future challenges include studying ectopic lipid fractions, the primary or secondary nature of mitochondrial dysfunction, and genetic-epigenetic factors.