title: Exposure to high levels of glucose increases the expression levels of genes involved in cholesterol biosynthesis in rat islets.
abstract: Cells continually adjust their gene expression profiles in order to adapt to the availability of nutrients. Glucose is a major regulator of pxancreatic β-cell function and cell growth. However, the mechanism of β-cell adaptation to high levels of glucose remains uncertain. To identify the specific targets responsible for adaptation to high levels of glucose, the differentially expressed genes from primary rat islets treated with 3.3 and 16.7 mmol/l glucose for 24 h were detected by DNA microarray. The results revealed that the expression levels of genes that encode enzymes required forde novocholesterol biosynthesis [3-hydroxy-3-methylglutaryl-CoA synthase 1 (Hmgcs1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), mevalonate (diphospho) decarboxylase (Mvd), isopentenyl-diphosphate δ-isomerase 1 (Idi1), squalene epoxidase (Sqle) and 7-dehydrocholesterol reductase (Dhcr7)] were significantly increased in islets treated with high levels of glucose compared with those in the islets treated with lower glucose levels. Quantitative polymerase chain reaction further confirmed that glucose stimulated the expression levels of these genes in a dose- and time-dependent manner. A similar result was obtained in islets isolated from rats subjected to 12, 24, 48 and 72 h of continuous glucose infusion. It has previously been recognized that cholesterol homeostasis is important for β-cell function. The present study provides, to the best of our knowledge, the first evidence for the involvement of thede novocholesterol biosynthesis pathway in the adaptation of rat islets to high levels of glucosein vitroandin vivo.
authors.affiliation: Department of Geratology, East Hospital, Shanghai Tongji University, Shanghai 200120, P.R. China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Geratology, East Hospital, Shanghai Tongji University, Shanghai 200120, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Geratology, East Hospital, Shanghai Tongji University, Shanghai 200120, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Shao
keywords: cholesterol biosynthesis; high glucose; nutrition adaptation; pancreatic β-cell