Fatehi-Hassanabad Zahra, Chan Catherine B
Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE C1A 4P3 Canada.
Nutr Metab (Lond). 2005 Jan 5;2(1):1. doi: 10.1186/1743-7075-2-1.
Optimal pancreatic beta-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 beta-cell function leading to elevated insulin secretion basally but with an impaired response to glucose. The transcription factors PPARalpha, PPARgamma 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 beta-cells and it appears that each may exert influence on beta-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.
最佳的胰腺β细胞功能对于人类和动物体内葡萄糖稳态的调节至关重要，其功能受损会导致糖尿病的发生。2型糖尿病是一种多基因疾病，会因缺乏体育活动或高热量高脂肪饮食等环境因素而加重。结果：游离脂肪酸是将过多脂肪量与2型糖尿病联系起来的一个重要因素。多项研究表明，长期升高的游离脂肪酸对β细胞功能有负面影响，导致基础胰岛素分泌增加，但对葡萄糖的反应受损。转录因子PPARα、PPARγ和SREBP-1c对组织中不断变化的脂肪浓度做出反应，从而协调基因组对代谢条件改变的反应，以促进脂肪储存或分解代谢。这些转录因子已在β细胞中被鉴定出来，似乎每种转录因子都可能在健康和疾病状态下对β细胞功能产生影响。结论：PPARs和SREBP-1c作为脂毒性潜在介质的作用是一个新兴的研究热点领域。
