Review

Transcriptional regulation of lipid metabolism by fatty acids: a key determinant of pancreatic β-cell function

Zahra Fatehi-Hassanabad and Catherine B Chan

Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE C1A 4P3 Canada

author email corresponding author email

Nutrition & Metabolism 2005, 2:1doi:10.1186/1743-7075-2-1

Published:	5 January 2005

Abstract

Background

Optimal pancreatic β-cell function is essential for the regulation of glucose homeostasis in both humans and animals and its impairment leads to the development of diabetes. Type 2 diabetes is a polygenic disease aggravated by environmental factors such as low physical activity or a hypercaloric high-fat diet.

Results

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 β-cell function leading to elevated insulin secretion basally but with an impaired response to glucose. The transcription factors PPARα, PPARγ 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 β-cells and it appears that each may exert influence on β-cell function in health and disease.

Conclusion

The role of the PPARs and SREBP-1c as potential mediators of lipotoxicity is an emerging area of interest.