Ikeda Kazuya, Tomimoto Shuhei, Tsuchiya Soken, Hamagami Ken-Ichi, Shintani Norihito, Sugimoto Yukihiko, Ichikawa Atsushi, Kasai Atsushi, Nakazawa Takanobu, Nagayasu Kazuki, Hayata-Takano Atsuko, Baba Akemichi, Hashimoto Hitoshi
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.
Biochem Biophys Rep. 2015 Jun 24;2:179-183. doi: 10.1016/j.bbrep.2015.06.006. eCollection 2015 Jul.
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 (KK) diabetic mice, and performed gene chip analysis of laser capture microdissected pancreatic islets from four F offspring genotypes (wild-type, PACAP-Tg, KK, and PACAP-Tg:KK). 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:KK mice compared with KK mice. These results may provide insight into the mechanisms of diabetes that accompany islet hyperplasia and amelioration by PACAP.
在糖尿病中，垂体腺苷酸环化酶激活多肽（PACAP）具有促胰岛素分泌和降血糖特性。我们之前证明，在胰腺β细胞中过表达PACAP的转基因小鼠（PACAP-Tg）在2型糖尿病模型中表现出胰腺胰岛增生和高胰岛素血症减轻。为了探究潜在机制，我们将PACAP-Tg小鼠与致死性黄色刺鼠（KK）糖尿病小鼠杂交，并对来自四种F后代基因型（野生型、PACAP-Tg、KK和PACAP-Tg:KK）的激光捕获显微切割的胰腺胰岛进行基因芯片分析。我们鉴定出1371个探针，在至少一对基因型之间存在>16倍的差异，并将这些探针分为具有特征性表达模式的五个簇。基因本体富集分析表明，与KK小鼠相比，在PACAP-Tg:KK小鼠中以基因上调为特征的簇中，参与核糖体和细胞内细胞器（如核糖核蛋白复合物、线粒体和染色体组织）相关术语的基因显著富集。这些结果可能为PACAP伴随的胰岛增生和改善相关糖尿病机制提供见解。
