Glucose-induced lipogenesis in pancreatic β-cells is dependent on SREBP-1

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• 作者：Maria B. Sandberg ; Jakob Fridriksson ; Lise Madsen ; Vikas Rishi ; Charles Vinson ; Holm Holmsen ; Rolf K. Berge and Susanne Mandrup
• 关键词：INS-1E cells ; Transduction ; Adenovirus ; Dominant negative SREBP ; Lipid accumulation ; Glucolipotoxicity
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2005
• 期刊代码：109_03037207
• 类别：bio
• 出版时间：2005
• 卷：240
• 期：1-2
• 页码：94-106
• 文件大小：487 K

摘要

High concentrations of glucose induce de novo fatty acid synthesis in pancreatic β-cells and chronic exposure of elevated glucose and fatty acids synergize to induce accumulation of triglycerides, a phenomenon termed glucolipotoxicity.

Here we investigate the role of sterol-regulatory element binding proteins in glucose-induced lipogenesis in the pancreatic β-cell line INS-1E. We show that glucose induces SREBP-1c expression and SREBP-1 activity independent of insulin secretion and signaling. Using adenoviral expression of SREBP-1c and a SREBP-mutant we show that lipogenic gene expression, de novo fatty acid synthesis and lipid accumulation are induced primarily through sterol-regulatory elements (SREs) and not E-Boxes. Adenoviral expression of a dominant negative SREBP compromises glucose induction of some lipogenic genes and significantly reduces glucose-induction of de novo fatty acid synthesis. Thus, we demonstrate for the first time that SREBP activity is necessary for full glucose induction of de novo fatty acid synthesis in pancreatic β-cells.