Yoshihiko Kaisho

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OBJECTIVE GPR40 is a G protein-coupled receptor regulating free fatty acid-induced insulin secretion. We generated transgenic mice overexpressing the hGPR40 gene under control of the mouse insulin II promoter and used them to examine the role of GPR40 in the regulation of insulin secretion and glucose homeostasis. RESEARCH DESIGN AND METHODS Normal(More)
The tissue distribution of neurotrophin-3 (NT-3) was investigated in rats at 1 month of age using a newly established, sensitive two-site enzyme immunoassay system for NT-3, as well as the immunocytochemical localization of this protein. The immunoassay for NT-3 enabled us to quantify NT-3 at levels > 3 pg per assay. In the rat brain, NT-3 was detectable(More)
A cDNA encoding a novel human neurotrophic factor (designated nerve growth factor-2; NGF-2) was cloned from a human glioma cDNA library using a synthetic DNA corresponding to human nerve growth factor (NGF). The cloned cDNA encodes a polypeptide composed of 257 amino acid residues including a prepro-sequence of 138 residues and a mature region of 119(More)
We compared the expression patterns of neurotrophin genes in the brain of senescence-accelerated mouse (SAMP8) which shows age-related impairment of learning behavior, with SAMR1 control which shows normal aging. By Northern blot analysis, NT-3 mRNA levels in the cortex were higher in SAMP8 than in SAMR1 mice during development, whereas in the midbrain,(More)
The developmental expression patterns of three members (NGF, NGF-2/NT-3, and BDNF) of the NGF family in rat brain are different. NGF-2/NT-3 mRNA was the first detected during development followed by NGF and BDNF mRNAs. A substantial amount of NGF mRNA was found to be synthesized in the hippocampus and the cortex, and this regional expression pattern did not(More)
Computer graphics indicate that a steric hindrance exists between valine-110 side chain of human lysozyme (EC 3.2.1.17) and an acetyl group of a modified substrate that contains N6,O-diacetylmuramic acid. To alter the substrate specificity of human lysozyme to be effective on the modified substrate, we replaced the valine-110 residue with various amino(More)
Levels of neurotrophin-3 (NT-3) in the mouse brain were measured by a highly sensitive enzyme immunoassay (EIA). The monoclonal antibody, 3W3, was labeled with beta-galactosidase, followed by measurement of galactosidase activity. The detection limit of the EIA system was 0.4 pg/well (4 pg/ml). At 1 and 8 weeks of age, the highest level of NT-3 was detected(More)
AIMS G protein-coupled receptor/free fatty acid receptor 1 (GPR40/FFAR1 ) regulates free fatty acid-induced insulin secretion. This study has been performed to clarify whether or not loss of GPR40/FFAR1 function exacerbates diabetes, that is, whether GPR40 has an essential physiological role in the development of diabetes or not. METHODS We generated(More)
We have replaced the NT-3 gene with Escherichia coli-derived lacZ gene by means of homologous recombination in embryonic stem cells and thus produced null mutant mice. Mice homozygous for this mutation developed to birth, but most of them could not suck well and died within 2 days after birth. The surviving homozygous mutant mice displayed movement disorder(More)
We replaced the neurotrophin-3 (NT-3) gene with Escherichia coli-derived lacZ via homologous recombination in embryonic stem (ES) cells and generated the mutant mice. Here we show the in vivo expression of NT-3 in the cerebellum during the postnatal period. A high level of lacZ expression was found in the granular layer of posterior lobe (lobules VII to X)(More)