Insulin resistance insulin
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Understanding Insulin Resistance: Mechanisms and Implications
Introduction to Insulin Resistance
Insulin resistance is a condition where the body's cells become less responsive to the hormone insulin, which is crucial for regulating blood glucose levels. This condition is a key factor in the development of several metabolic diseases, including type 2 diabetes and cardiovascular disease1 2 4. Insulin resistance is characterized by a reduced ability of insulin to stimulate glucose uptake in tissues such as muscle, fat, and liver1 2.
Causes and Mechanisms of Insulin Resistance
Genetic and Environmental Factors
The development of insulin resistance is influenced by a combination of genetic predispositions and environmental factors. Obesity, particularly the accumulation of visceral fat, is a significant contributor to insulin resistance1 6 9. Genetic factors can predispose individuals to insulin resistance, but lifestyle factors such as diet and physical inactivity play a crucial role in its manifestation5 7.
Molecular Mechanisms
At the molecular level, insulin resistance involves disruptions in the insulin signaling pathway. Key components affected include the insulin receptor, insulin receptor substrate (IRS) proteins, and AKT, a protein kinase involved in glucose uptake1 6. Ectopic lipid accumulation in tissues like the liver and skeletal muscle, endoplasmic reticulum stress, and inflammation are also significant contributors to insulin resistance2 6 8.
Role of Adipose Tissue
Adipose tissue plays a critical role in the development of insulin resistance by releasing lipids and other factors that interfere with insulin signaling in other organs. This can lead to the accumulation of harmful intermediates such as ceramides, which inhibit insulin action1 6 8.
Clinical Implications of Insulin Resistance
Metabolic Diseases
Insulin resistance is a central feature of metabolic syndrome, which includes conditions like type 2 diabetes, hypertension, and nonalcoholic fatty liver disease6 7 9. It is also associated with an increased risk of cardiovascular diseases due to its role in promoting hyperglycemia and hyperlipidemia4 10.
Type 1 Diabetes
While primarily associated with type 2 diabetes, insulin resistance is also present in type 1 diabetes and contributes to its complications. Addressing insulin resistance in type 1 diabetes is crucial for reducing the risk of vascular complications3.
Therapeutic Strategies
Lifestyle Modifications
Lifestyle changes, including increased physical activity and dietary modifications, are fundamental in managing insulin resistance. These interventions help reduce fat mass and improve insulin sensitivity7 8.
Pharmacological Treatments
Several pharmacological agents are used to improve insulin sensitivity. Metformin and thiazolidinediones are well-established treatments, while newer therapies such as incretin mimetics and sodium-glucose cotransporter inhibitors show promise3 7 8.
Emerging Therapies
Research is ongoing to develop novel therapies targeting specific molecular pathways involved in insulin resistance. These include targeting bioactive lipids, endoplasmic reticulum stress, and inflammatory mediators6 8.
Conclusion
Insulin resistance is a complex condition with multifaceted causes and significant implications for metabolic health. Understanding its mechanisms is crucial for developing effective treatments and managing associated diseases. Continued research is essential to uncover new therapeutic targets and improve patient outcomes.
Sources and full results
Most relevant research papers on this topic
The aetiology and molecular landscape of insulin resistance
Insulin resistance is a complex disorder caused by genetic and environmental factors, with adipose tissue playing a key role in its development.
Highly CitedInsulin Resistance: From Mechanisms to Therapeutic Strategies
Insulin resistance is linked to ectopic lipid accumulation, endoplasmic reticulum stress, and inflammation, and potential therapeutic strategies include addressing these mechanisms and promoting glucose metabolism.
Very Rigorous JournalHighly CitedAddressing insulin resistance in Type 1 diabetes
Insulin resistance in Type 1 diabetes contributes to the development of complications and may be treated with safe and effective measures, such as metformin.
Systematic ReviewVery Rigorous JournalHighly CitedInsulin Resistance: Cellular and Clinical Concepts
Insulin resistance occurs years before clinical hyperglycemia and Type 2 diabetes diagnosis, and is associated with accelerated cardiovascular disease risk factors.
Highly CitedInsulin and insulin resistance.
Insulin resistance, influenced by physical inactivity and dietary imbalances, plays a significant role in obesity and diabetes epidemics in Westernized populations.
Highly CitedMechanisms of Insulin Action and Insulin Resistance.
This review aims to understand insulin action and resistance, which are key factors in type 2 diabetes, to guide the development of novel therapies for the condition.
Highly CitedThe crucial role and mechanism of insulin resistance in metabolic disease
Insulin resistance contributes to the development of metabolic diseases like diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, with treatments mainly focusing on exercise, dietary habits, and chemotherapy.
Systematic ReviewHighly CitedInsulin resistance and insulin sensitizing agents.
Insulin resistance in obesity and type 2 diabetes is linked to dysfunctional adipose tissue, glucotoxicity, oxidative stress, and inflammation, with lifestyle modification, bariatric surgery, and new antihyperglycemic drugs helping to improve insulin sensitivity.
Highly CitedThe Origins and Drivers of Insulin Resistance
Insulin resistance is a complex, multifactorial condition influenced by inflammation, lipid metabolism, and gut microbiota, with obesity being the major contributing factor.
Highly CitedResolving the Paradox of Hepatic Insulin Resistance
The interplay between intrahepatic and extrahepatic pathways controls insulin signaling, leading to paradoxical effects in insulin-resistant livers rather than deficiencies in only the direct hepatic pathway.
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