This article discusses the role of mitochondrial dysfunction and insulin resistance in the development of type 2 diabetes. It highlights the importance of understanding the mechanisms behind insulin resistance, which is a key factor in the pathogenesis of the metabolic syndrome and type 2 diabetes. The article reviews recent studies that have identified insulin-stimulated glucose transport defects in skeletal muscle as a primary metabolic abnormality in insulin-resistant patients with type 2 diabetes. These defects are thought to be caused by fatty acids inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. The article also explores the role of fatty acids in causing insulin resistance in muscle cells, and how they can interfere with glucose transport and phosphorylation activity. It discusses the impact of increased energy intake and obesity on insulin resistance, as well as the role of defects in adipocyte fatty acid metabolism in causing insulin resistance. The article also addresses mitochondrial dysfunction as a contributing factor to insulin resistance, and how it can lead to the accumulation of intracellular fatty acid metabolites, which in turn can impair insulin signaling. Additionally, the article discusses interventions that can reverse insulin resistance, such as exercise, diet, and pharmacologic treatments. It emphasizes the importance of understanding the molecular and biochemical defects responsible for insulin resistance in order to develop new therapeutic targets for the treatment of the metabolic syndrome and type 2 diabetes. The article concludes by highlighting the need for further research into the key cellular mechanisms of insulin resistance to improve the prevention and treatment of type 2 diabetes.This article discusses the role of mitochondrial dysfunction and insulin resistance in the development of type 2 diabetes. It highlights the importance of understanding the mechanisms behind insulin resistance, which is a key factor in the pathogenesis of the metabolic syndrome and type 2 diabetes. The article reviews recent studies that have identified insulin-stimulated glucose transport defects in skeletal muscle as a primary metabolic abnormality in insulin-resistant patients with type 2 diabetes. These defects are thought to be caused by fatty acids inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. The article also explores the role of fatty acids in causing insulin resistance in muscle cells, and how they can interfere with glucose transport and phosphorylation activity. It discusses the impact of increased energy intake and obesity on insulin resistance, as well as the role of defects in adipocyte fatty acid metabolism in causing insulin resistance. The article also addresses mitochondrial dysfunction as a contributing factor to insulin resistance, and how it can lead to the accumulation of intracellular fatty acid metabolites, which in turn can impair insulin signaling. Additionally, the article discusses interventions that can reverse insulin resistance, such as exercise, diet, and pharmacologic treatments. It emphasizes the importance of understanding the molecular and biochemical defects responsible for insulin resistance in order to develop new therapeutic targets for the treatment of the metabolic syndrome and type 2 diabetes. The article concludes by highlighting the need for further research into the key cellular mechanisms of insulin resistance to improve the prevention and treatment of type 2 diabetes.