Chronic Activation of Liver X Receptor Induces β-Cell Apoptosis Through Hyperactivation of Lipogenesis

• DOI: 10.2337/db06-1059
• Publication Date: 2007-05-26T03:53:57Z
• Authors: Sung Sik Choe; A Hyun Choi; Joo-Won Lee; Kang Ho Kim; Jun-Jae Chung; Jiyoung Park; Kyeong-Min Lee; Keun-Gyu Park; In-Kyu Lee; Jae Bum Kim
• Keywords: Lipotoxicity; Liver X receptor; Lipogenesis; Pancreatic Islets

Liver X receptor (LXR)α and LXRβ play important roles in fatty acid metabolism cholesterol homeostasis. Although the functional of LXR liver, intestine, fat, macrophages are well established, its role pancreatic β-cells has not been clearly defined. In this study, we revealed that chronic activation contributes to lipotoxicity-induced β-cell dysfunction. We observed significantly elevated expression islets diabetic rodent models, including fa/fa ZDF rats, OLETF db/db mice. primary INS-1 insulinoma cells, with a synthetic ligand, T0901317, stimulated lipogenic genes ADD1/SREBP1c, FAS, ACC resulted increased intracellular lipid accumulation. Moreover, induced apoptosis which was synergistically promoted by high glucose conditions. Taken together, suggest accumulation caused as possible cause lipotoxicity, key step development type 2 diabetes.