Insulin Resistance: Molecular Mechanisms of Signalling, Pathophysiological Impact
DOI:
https://doi.org/10.59675/M414Keywords:
Insulin resistance, insulin signalling, IRS/PI3K/Akt, Inflammation, Oxidative stress.Abstract
Background: Insulin resistance is a complicated metabolic state in which the body does not respond to insulin properly and is related to abnormalities in glucose and lipid metabolism and to various metabolic and cardiometabolic disorders. Insulin resistance involves molecular mechanisms that are critical to understanding, improving diagnosis, and identifying potential therapeutic targets.
Methods: We reviewed the molecular and pathophysiological mechanisms of insulin resistance and their implications for metabolic and systemic disorders. We searched PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for publications from January 2000 to September 2026. We reviewed the literature for insulin signalling, lipid metabolism, inflammation, oxidative stress, mitochondrial and endoplasmic reticulum dysfunction, insulin resistance in different tissues, insulin resistance and related diseases, and diagnostic and therapeutic potential.
Results: The evidence reviewed here suggests that insulin signalling problems (especially alterations in the IRS/PI3K/Akt pathway) play an important role in inducing insulin resistance through interactions with lipotoxicity, chronic inflammation, oxidative stress, mitochondrial dysfunction, and impaired inter-organ communication. These mechanisms lead to glucose and lipid abnormalities and have been linked to type 2 diabetes and to other cardiometabolic and systemic disorders such as cardiovascular disease, fatty liver disease, hypertension, polycystic ovary syndrome, and chronic kidney disease. Assessment techniques range from simple surrogate measures like HOMA-IR and QUICKI to more dynamic methods like the euglycemic–hyperinsulinemic clamp, depending on the clinical or research context.
Conclusion: Insulin resistance is a disorder that is more complex and tissue-specific than originally thought to be a single linear metabolic defect. Enhanced integration of molecular mechanisms with clinical evidence will help identify clinically relevant biomarkers and targets. New strategies targeting insulin signalling, lipid metabolism, inflammation, and related metabolic pathways are promising and warrant further exploration for clinical efficacy.
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