title: Sfrp5 mediates glucose-induced proliferation in rat pancreatic β-cells.
abstract: The cellular and molecular mechanisms of glucose-stimulated β-cell proliferation are poorly understood. Recently, secreted frizzled-related protein 5 (encoded by Sfrp5; a Wnt signaling inhibitor) has been demonstrated to be involved in β-cell proliferation in obesity. A previous study demonstrated that glucose enhanced Wnt signaling to promote cell proliferation. We hypothesized that inhibition of SFRP5 contributes to glucose-stimulated β-cell proliferation. In this study, we found that the Sfrp5 level was significantly reduced in high glucose-treated INS-1 cells, primary rat β-cells, and islets isolated from glucose-infused rats. Overexpression of SFRP5 diminished glucose-stimulated proliferation in both INS-1 cells and primary β-cells, with a concomitant inhibition of the Wnt signaling pathway and decreased cyclin D2 expression. In addition, we showed that glucose-induced Sfrp5 suppression was modulated by the PI3K/AKT pathway. Therefore, we conclude that glucose inhibits Sfrp5 expression via the PI3K/AKT pathway and hence promotes rat pancreatic β-cell proliferation.
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China Department of EndocrinologyFuJian Union hospital, Fuzhou, P R China.
authors: Binbin
authors: B
authors: Guan
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Wenyi
authors: W
authors: Li
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Fengying
authors: F
authors: Li
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Yun
authors: Y
authors: Xie
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Qicheng
authors: Q
authors: Ni
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Yanyun
authors: Y
authors: Gu
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Xiaoying
authors: X
authors: Li
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Qidi
authors: Q
authors: Wang
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China hongliting@sina.com.
authors: Hongli
authors: H
authors: Zhang
authors: Shanghai Institute of Endocrine and Metabolic DiseasesShanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China.
authors: Guang
authors: G
authors: Ning
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D056742:Cyclin D2 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D054392:Adipokines; D056742:Cyclin D2; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C486197:Ccnd2 protein, rat; C000608752:sFRP5 protein, rat; D000094742:Secreted Frizzled-Related Proteins
keywords: Sfrp5; glucose; proliferation; β-cell