title: The effect of cholesteryl ester transfer protein on pancreatic beta cell dysfunction in mice.
abstract: BACKGROUND
  Cholesterol accumulation causes pancreatic beta cell lipotoxicity and dysfunction. Cholesteryl ester transfer protein (CETP) plays an important role in blood lipid homeostasis. However, its role in tissue lipid metabolism remains unclear. We hypothesized that plasma CETP impact cholesterol homeostasis in the beta cells, thus damaging their functions.
  
  
  METHODS
  The adipose tissue-specific CETP expression transgenic (aP2-CETPTg) mice, characterized by high CETP levels in the circulation, were used in this study. Pancreatic islet cholesterol and beta cell function were assessed in mice. We further measured mRNA levels of the genes involved in beta cell proliferation and differentiation, inflammation and cholesterol metabolism. TUNEL assay was applied to investigate beta cell apoptosis in islets.
  
  
  RESULTS
  The aP2-CETPTg mice exhibited glucose intolerance, lower plasma insulin concentrations but increased insulin sensitivity compared with wild type mice. In addition, glucose-stimulated insulin secretion from isolated pancreatic islets significantly decreased, and free cholesterol significantly increased. Moreover, the number and size of islets from aP2-CETPTg mice were significantly decreased. Genes involved in beta cell proliferation, such as Pdx1 and BETA2, were down-regulated; genes involved in inflammation and ER stress, such as IL-1β, CHOP, and Xbp1 were up-regulated, in line with an increase of beta cell apoptosis.
  
  
  CONCLUSIONS
  Plasma CETP causes free cholesterol accumulation in islets which could contribute to beta cell dysfunction. Thus, CETP inhibition could be a novel protective strategy for dyslipidemia related to diabetes and obese.
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Yingyun
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Xianxia
authors.initials: X
authors.lastname: Ju
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhou
keywords: Beta cell function; Cholesterol ester transfer protein; Free cholesterol; Glucose metabolism