Phosphatidylinositol-3,4,5-triphosphate and cellular signaling: implications for obesity and diabetes

Abstract

Phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P₃) is one of the most important phosphoinositides and is capable of activating a wide range of proteins through its interaction with their specific binding domains. Localization and activation of these effector proteins regulate a number of cellular functions, including cell survival, proliferation, cytoskeletal rearrangement, intracellular vesicle trafficking, and cell metabolism. Phosphoinositides have been investigated as an important agonist-dependent second messenger in the regulation of diverse physiological events depending upon the phosphorylation status of their inositol group. Dysregulation in formation as well as metabolism of phosphoinositides is associated with various pathophysiological disorders such as inflammation, allergy, cardiovascular diseases, cancer, and metabolic diseases. Recent studies have demonstrated that the impaired metabolism of PtdIns(3,4,5)P₃ is a prime mediator of insulin resistance associated with various metabolic diseases including obesity and diabetes. This review examines the current status of the role of PtdIns(3,4,5)P₃ signaling in the regulation of various cellular functions and the implications of dysregulated PtdIns(3,4,5)P₃ signaling in obesity, diabetes, and their associated complications.