%0 Journal Article
%T Transcriptional regulation of lipid metabolism by fatty acids: a key determinant of pancreatic ¦Â-cell function
%A Zahra Fatehi-Hassanabad
%A Catherine B Chan
%J Nutrition & Metabolism
%D 2005
%I BioMed Central
%R 10.1186/1743-7075-2-1
%X Free fatty acids represent an important factor linking excess fat mass to type 2 diabetes. Several studies have shown that chronically elevated free fatty acids have a negative effect on ¦Â-cell function leading to elevated insulin secretion basally but with an impaired response to glucose. The transcription factors PPAR¦Á, PPAR¦Ã and SREBP-1c respond to changing fat concentrations in tissues, thereby coordinating the genomic response to altered metabolic conditions to promote either fat storage or catabolism. These transcription factors have been identified in ¦Â-cells and it appears that each may exert influence on ¦Â-cell function in health and disease.The role of the PPARs and SREBP-1c as potential mediators of lipotoxicity is an emerging area of interest.Fatty acids are physiologically important both structurally, as components of phospholipids and glycolipids, as well as functionally, as fuel molecules. Metabolites of fatty acids, such as leukotrienes or prostaglandins, act as potent mediators in many biological processes. Fatty acids provide energy [1,2], particularly in the fasted state (Figure 1), but abnormalities in the metabolism of fatty acids can contribute to the pathogenesis of obesity and type 2 diabetes.Diabetes affects 6 % of the adult population and, with a growth rate of 6% per year, it is estimated that 200 to 300 million people worldwide will be afflicted by the end of this decade [3]. Type 1 diabetes, which accounts for < 10 % of all cases of diabetes [4], results from autoimmune-mediated destruction of pancreatic ¦Â-cells. The destruction may occur over months to years and can result in complete loss of the endogenous insulin supply and therefore results in exogenous insulin dependency.Type 2 diabetes, which accounts for 90 to 95 % of diabetes cases worldwide, is a heterogeneous disorder and its prevalence is rising. Type 2 diabetes is accompanied by chronic insulin resistance and a progressive decline in ¦Â-cell function [5]. Obesity is a major ri
%U http://www.nutritionandmetabolism.com/content/2/1/1