title: Phosphoinositide signalling in type 2 diabetes: a β-cell perspective.
abstract: Type 2 diabetes is a complex disease. It results from a failure of the body to maintain energy homoeostasis. Multicellular organisms have evolved complex strategies to preserve a relatively stable internal nutrient environment, despite fluctuations in external nutrient availability. This complex strategy involves the co-ordinated responses of multiple organs to promote storage or mobilization of energy sources according to the availability of nutrients and cellular bioenergetics needs. The endocrine pancreas plays a central role in these processes by secreting insulin and glucagon. When this co-ordinated effort fails, hyperglycaemia and hyperlipidaemia develops, characterizing a state of metabolic imbalance and ultimately overt diabetes. Although diabetes is most likely a collection of diseases, scientists are starting to identify genetic components and environmental triggers. Genome-wide association studies revealed that by and large, gene variants associated with type 2 diabetes are implicated in pancreatic β-cell function, suggesting that the β-cell may be the weakest link in the chain of events that results in diabetes. Thus, it is critical to understand how environmental cues affect the β-cell. Phosphoinositides are important 'decoders' of environmental cues. As such, these lipids have been implicated in cellular responses to a wide range of growth factors, hormones, stress agents, nutrients and metabolites. Here we will review some of the well-established and potential new roles for phosphoinositides in β-cell function/dysfunction and discuss how our knowledge of phosphoinositide signalling could aid in the identification of potential strategies for treating or preventing type 2 diabetes.
authors: Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, U.S.A. rameh@bu.edu.
authors: Lucia E
authors: LE
authors: Rameh
authors: Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, U.S.A.
authors: Jude T
authors: JT
authors: Deeney
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007328:Insulin; D010716:Phosphatidylinositols; D019870:1-Phosphatidylinositol 4-Kinase
keywords: insulin; lipid kinases; nutrients; obesity; signalling; β-cell