Diabetes and the role of inositol-containing lipids in insulin signaling.
Among metabolic diseases, diabetes is considered one of the most prevalent throughout the world. Currently, statistics show that over 10% of the world's aged population (60 years and older) suffers from diabetes. As a consequence, it consumes a considerable proportion of world health expenditure. This review considers both past and current research into the molecular basis of insulin resistance found in type II diabetes and focuses on the role of inositol-containing phospholipid metabolism. It has been firmly established that the activation of phosphatidylinositol 3-kinase (PI3-K) is important for the propagation of the metabolic actions of insulin. In addition to the 3-phosphorylated phosphatidylinositols formed via the action of PI3-K, the glycosyl-phosphatidylinositol/inositol phosphoglycan (GPI/IPG) signaling component is also strongly implicated in mediating numerous metabolic actions of insulin. Although all the elements within the type II diabetes phenotype have not been fully defined, it has been proposed that defects in insulin transmembrane signaling through malfunction of inositol-containing phospholipid metabolism and absenteeism of the generation of phospholipid-derived second messengers may be associated with the appearance of the type II diabetic phenotype. Pharmaceutical approaches using synthetically produced IPG analogues, which themselves mimic insulin's actions, alone or in combination with other drugs, may lead the way toward introducing alternative therapies for type II diabetes in the coming years.
Jones
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DR
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid, Spain. djones@cnb.uam.es
Varela-Nieto
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I
D000368:Aged; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D015995:Prevalence; D015398:Signal Transduction
D007328:Insulin; D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases