A High-Fat/High-Sucrose Diet Induces WNT4 Expression in Mouse Pancreatic β-cells

作者：Yayoi Kurita, Tsuyoshi Ohki, Eri Soejima, Xiaohong Yuan, Satomi Kakino, Nobuhiko Wada, Toshihiko Hashinaga, Hitomi Nakayama, Junichi Tani, Yuji Tajiri, Yuji Hiromatsu, Kentaro Yamada, Masatoshi Nomura · 发表于：The Kurume Medical Journal · 年份：2018 · DOI：10.2739/kurumemedj.ms652008 · 被引用次数：22 · 研究领域：Pancreatic function and diabetes、Aldose Reductase and Taurine、Wnt/β-catenin signaling in development and cancer

Aims/Introduction: Several lines of evidence suggest that dysregulation of the WNT signaling pathway is involved in the pathogenesis of type 2 diabetes. This study was performed to elucidate the effects of a high-fat/high-sucrose (HF/HS) diet on pancreatic islet functions in relation to modulation of WNT ligand expression in β-cells. MATERIALS AND METHODS: Mice were fed either standard mouse chow or a HF/HS diet from 8 weeks of age. At 20 weeks of age, intraperitoneal glucose tolerance tests were performed in both groups of mice, followed by euthanasia and isolation of pancreatic islets. WNT-related gene expression in islets and MIN6 cells was measured by quantitative real-time RT-PCR. To explore the direct effects of WNT signals on pancreatic β-cells, MIN6 cells were exposed to recombinant mouse WNT4 protein (rmWNT4) for 48 h, and glucose-induced insulin secretion was measured. Furthermore, Wnt4 siRNAs were transfected into MIN6 cells, and cell viability and insulin secretion were measured in control and Wnt4 siRNA-transfected MIN6 cells. RESULTS: Mice fed the HF/HS diet were heavier and their plasma glucose and insulin levels were higher compared with mice fed standard chow. Wnt4, Wnt5b, Ror1, and Ror2 expression was upregulated, while Fzd4, Fzd5, Fzd6, Lrp5, and Lrp6 expression was downregulated in the islets of mice fed the HF/HS diet. Wnt4 was the most abundantly expressed WNT ligand in β-cells, and its expression was increased by the HF/HS diet. Although exposure to rec...