Comparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice

Kazuya Ikeda; Shuhei Tomimoto; Soken Tsuchiya; Ken-Ichi Hamagami; Norihito Shintani; Yukihiko Sugimoto; Atsushi Ichikawa; Atsushi Kasai; Takanobu Nakazawa; Kazuki Nagayasu; Atsuko Hayata-Takano; Akemichi Baba; Hitoshi Hashimoto

doi:10.1016/j.bbrep.2015.06.006

Comparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice

Biochem Biophys Rep. 2015 Jun 24:2:179-183. doi: 10.1016/j.bbrep.2015.06.006. eCollection 2015 Jul.

Authors

Kazuya Ikeda^{1

2}, Shuhei Tomimoto¹, Soken Tsuchiya^{3

4}, Ken-Ichi Hamagami¹, Norihito Shintani¹, Yukihiko Sugimoto^{3

4}, Atsushi Ichikawa^{3

5}, Atsushi Kasai¹, Takanobu Nakazawa⁶, Kazuki Nagayasu⁶, Atsuko Hayata-Takano⁷, Akemichi Baba^{1

8}, Hitoshi Hashimoto^{1

6

7}

Affiliations

¹ Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
² Research Fellow of the Japan Society for the Promotion of Science, Japan.
³ Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
⁴ Department of Pharmaceutical Biochemistry, Kumamoto University Graduate School of Pharmaceutical Sciences, Oe-Honmachi, Kumamoto 862-0973, Japan.
⁵ Institute for Biosciences, Mukogawa Women's University, 11-68 Koshien-Kyubancho, Nishinomiya-shi, Hyogo 663-8179, Japan.
⁶ 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.
⁷ 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.
⁸ Faculty of Pharmaceutical Sciences, Hyogo University of Health Science, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan.

Abstract

In diabetes mellitus, pituitary adenylate cyclase-activating polypeptide (PACAP) has insulinotropic and glucose-lowering properties. We previously demonstrated that transgenic mice overexpressing PACAP in pancreatic β-cells (PACAP-Tg) show attenuated pancreatic islet hyperplasia and hyperinsulinemia in type 2 diabetic models. To explore the underlying mechanisms, here we crossed PACAP-Tg mice with lethal yellow agouti (KKAy) diabetic mice, and performed gene chip analysis of laser capture microdissected pancreatic islets from four F₁ offspring genotypes (wild-type, PACAP-Tg, KKAy, and PACAP-Tg:KKAy). We identified 1371 probes with >16-fold differences between at least one pair of genotypes, and classified the probes into five clusters with characteristic expression patterns. Gene ontology enrichment analysis showed that genes involved in the terms ribosome and intracellular organelles such as ribonucleoprotein complex, mitochondrion, and chromosome organization were significantly enriched in clusters characterized by up-regulated genes in PACAP-Tg:KKAy mice compared with KKAy mice. These results may provide insight into the mechanisms of diabetes that accompany islet hyperplasia and amelioration by PACAP.

Keywords: Chromosome; GO, gene ontology; Gene expression; KKAy mice, lethal yellow agouti diabetic mice; Lethal yellow agouti (KKAy) diabetic mice; Mitochondrion; PACAP; PACAP, pituitary adenylate cyclase-activating polypeptide; PACAP-Tg mice, transgenic mice overexpressing PACAP in pancreatic β-cells; Ribosome.