First published online August 29, 2005
Journal of Cell Science 118, 1702e (2005)
© The Company of Biologists Limited
SREBP stressed out by glucose
In type II diabetes, high levels of blood glucose and lipids are thought to lead to reduced insulin secretion and the destruction of pancreatic ß-cells. The molecular basis for this glucolipotoxicity is obscure, but it might involve transcription factors that regulate lipid metabolism. Haiyan Wang and co-workers have therefore examined the role of steroid-response-element-binding protein (SREBP), a lipogenic transcription factor induced in many animal models of diabetes (p. 3905). They demonstrate that treatment with high levels of glucose and expression of SREBP-1c have markedly similar affects on INS-1 insulinoma cells: both lead to lipid accumulation and apoptosis, and they produce similar gene expression profiles. By generating a stable cell line expressing a dominant negative mutant of SREBP-1c, the authors are able to show that the transcription factor is required for the glucolipotoxic effects of high glucose levels. Significantly, they also find that high glucose levels in INS-1 cells cause ER stress. Since this phenomenon has a well-established role in proteolytic activation of SREBP, a pathway in which hyperglycaemia and hyperlipidaemia induce ER stress and consequent SREBP activation could be critical feature of the pathogenesis of type II diabetes.
Related articles in JCS:
- ER stress and SREBP-1 activation are implicated in ß-cell glucolipotoxicity
- Haiyan Wang, Georgia Kouri, and Claes B. Wollheim
JCS 2005 118: 3905-3915.
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