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Abstract: To investigate the role of liver-specific expression of glucokinase (GCK) in the pathogenesis of hyperglycemia and to identify candidate genes involved in mechanisms of the onset and progression of maturity onset diabetes of the young, type 2 (MODY-2), we examined changes in biochemical parameters and gene expression in GCK knockout (gckw/–) and wild-type (gckw/w) mice as they aged. Fasting blood glucose levels were found to be significantly higher in the gckw/– mice, compared to age-matched gckw/w mice, at all ages (P <0.05), except at 2weeks. GCK activity of gckw/– mice was about 50% of that of wild type (gckw/w) mice (P <0.05). Glycogen content at 4 and 40weeks of age was lower in gckw/– mice compared to gckw/w mice. Differentially expressed genes in the livers of 2 and 26week-old liver-specific GCK knockout (gckw/–) mice were identified by suppression subtractive hybridization (SSH), which resulted in the identification of phosphoenolpyruvatecarboxykinase (PEPCK, also called PCK1) and Sterol O-acyltransferase 2 (SOAT2) as candidate genes involved in pathogenesis. The expressions of PEPCK and SOAT2 along with glycogen phosphorylase (GP) and glycogen synthase (GS) were then examined in GCK knockout (gckw/–) and wild-type (gckw/w) mice at different ages. Changes in PEPCK mRNA levels were confirmed by real-time RT-PCR, while no differences in the levels of expression of SOAT2 or GS were observed in age-matched GCK knockout (gckw/–) and wild-type (gckw/w) mice. GP mRNA levels were decreased in 40-week old gckw/– mice compared to age-matched gckw/w mice. Changes in gluconeogenesis, delayed development of GCK and impaired hepatic glycogen synthesis in the liver potentially lead to the onset and progression of MODY2. [Copyright &y& Elsevier]

• It is a novel report on the effects of BPA on ovarian development in adolescent mice. • 4266 differentially expressed genes (DEGs) in the ovary of adolescent mice due to BPA exposure were identified by RNA-Seq. • BPA exposure has far-reaching effects on ovarian development in adolescent mice. Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways. [ABSTRACT FROM AUTHOR]