p13 overexpression in pancreatic β-cells ameliorates type 2 diabetes in high-fat-fed mice

Shintaro Higashi; Kazuhiko Katagi; Norihito Shintani; Kazuya Ikeda; Yukihiko Sugimoto; Soken Tsuchiya; Naoki Inoue; Shota Tanaka; Mai Koumoto; Atsushi Kasai; Takanobu Nakazawa; Atsuko Hayata-Takano; Ken-Ichi Hamagami; Shuhei Tomimoto; Takuya Yoshida; Tadayasu Ohkubo; Kazuki Nagayasu; Yukio Ago; Yusuke Onaka; Ryota Hashimoto; Atsushi Ichikawa; Akemichi Baba; Hitoshi Hashimoto

doi:10.1016/j.bbrc.2015.04.074

p13 overexpression in pancreatic β-cells ameliorates type 2 diabetes in high-fat-fed mice

Biochem Biophys Res Commun. 2015 Jun 12;461(4):612-7. doi: 10.1016/j.bbrc.2015.04.074. Epub 2015 Apr 23.

Authors

Shintaro Higashi¹, Kazuhiko Katagi², Norihito Shintani³, Kazuya Ikeda¹, Yukihiko Sugimoto⁴, Soken Tsuchiya⁴, Naoki Inoue², Shota Tanaka², Mai Koumoto², Atsushi Kasai², Takanobu Nakazawa⁵, Atsuko Hayata-Takano⁶, Ken-Ichi Hamagami², Shuhei Tomimoto², Takuya Yoshida⁷, Tadayasu Ohkubo⁷, Kazuki Nagayasu⁵, Yukio Ago⁸, Yusuke Onaka⁹, Ryota Hashimoto¹⁰, Atsushi Ichikawa¹¹, Akemichi Baba¹², Hitoshi Hashimoto¹³

Affiliations

¹ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Research Fellow of the Japan Society for the Promotion of Science, Japan.
² Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
³ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Biology, University of Padua, 35121 Padua, Italy.
⁴ Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
⁵ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁶ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁷ Laboratory of Biophysical Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁸ Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁹ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Research Fellow of the Japan Society for the Promotion of Science, Japan; Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
¹⁰ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Psychiatry, Graduate School of Medicine, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
¹¹ Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; Institute for Biosciences, Mukogawa Women's University, Kyu-ban cho, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
¹² Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Faculty of Pharmaceutical Sciences, Hyogo University of Health Science, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan. Electronic address: akbaba@huhs.ac.jp.
¹³ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: hasimoto@phs.osaka-u.ac.jp.

PMID: 25912136
DOI: 10.1016/j.bbrc.2015.04.074

Abstract

We examined the pancreatic function of p13 encoded by 1110001J03Rik, whose expression is decreased in pancreatic islets in high-fat-fed diabetic mice, by generating transgenic mice overexpressing p13 (p13-Tg) in pancreatic β-cells. p13-Tg mice showed normal basal glucose metabolism; however, under high-fat feeding, these animals showed augmented glucose-induced first-phase and total insulin secretion, improved glucose disposal, greater islet area and increased mitotic insulin-positive cells. In addition, high-fat diet-induced 4-hydroxynonenal immunoreactivity, a reliable marker and causative agent of lipid peroxidative stress, was significantly decreased in p13-Tg mouse islets. These results indicate that p13 is a novel pancreatic factor exerting multiple beneficial effects against type 2 diabetes.

Keywords: 1110001J03Rik; Glucose-induced insulin secretion; High-fat diet; Lipid peroxidative stress; PACAP; Type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Type 2 / metabolism*
Diet, High-Fat*
Insulin-Secreting Cells / metabolism*
Mice
Mice, Transgenic
Obesity / metabolism*
Up-Regulation