biostudies-literatureIkeda KJSPS Program for Advancing Strategic International NetworksUehara Memorial FoundationJSPS Research Fellowships for Young ScientistsPancreas Research Foundation of JapanJapan Society for the Promotion of Science179-183https://www.ebi.ac.uk/biostudies/studies/S-EPMC5668656biostudies-literatureUnknown2In 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.Biochemistry and biophysics reportsComparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice.PMC5668656S2603Tomimoto STsuchiya SHamagami KINakazawa TIchikawa ANagayasu KSugimoto YIkeda KShintani NBaba AKasai AHayata-Takano AHashimoto HfalseComparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice.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.2015-01-01T00:00:00Z2015 Jul2024-11-10T00:58:22.673Z2019-03-27T03:00:48ZS-EPMC56686562912416110.1016/j.bbrep.2015.06.006