A5024368247- Calcium signaling and nucleotide metabolism
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- Ion Channels and Receptors
- Diabetes and associated disorders
- Neuroscience of respiration and sleep
- Obstructive Sleep Apnea Research
- Advanced Glycation End Products research
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Helicobacter pylori-related gastroenterology studies
- Neonatal Health and Biochemistry
- Cancer-related molecular mechanisms research
- Pancreatitis Pathology and Treatment
- PARP inhibition in cancer therapy
- Salivary Gland Disorders and Functions
- Signaling Pathways in Disease
- Digestive system and related health
- Ion channel regulation and function
- RNA modifications and cancer
- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
Nara Medical University
2016-2025
Nara Medical University Hospital
2011-2014
Tohoku University
2002-2013
China Medical University
2011
Kanagawa Prefectural Hospital Organization
2011
Kanagawa Cancer Center
2011
Kouseiren Takaoka Hospital
2011
Yamagata University
2001
Stanford University
2001
Yamaguchi University
2000
The binding of advanced glycation end-products (AGE) to the receptor for AGE (RAGE) is known deteriorate various cell functions and implicated in pathogenesis diabetic vascular complications. In present study, we show that cellular constituents small vessels, endothelial cells (EC) pericytes express novel splice variants RAGE mRNA coding isoforms lack N-terminal V-type immunoglobulin-like domain (N-truncated) or C-terminal transmembrane (C-truncated), as well full-length mRNA. ratio...
Vascular complications arising from multiple environmental and genetic factors are responsible for many of the disabilities short life expectancy associated with diabetes mellitus. Here we provide first direct in vivo evidence that interactions between advanced glycation end products (AGEs; nonenzymatically glycosylated protein derivatives formed during prolonged hyperglycemic exposure) their receptor, RAGE, lead to diabetic vascular derangement. We created transgenic mice overexpress human...
Administration of poly(ADP-ribose) synthetase inhibitors such as nicotinamide to 90% depancreatized rats induces regeneration pancreatic islets, thereby ameliorating the surgical diabetes (Yonemura, Y.,
Inositol 1,4,5-trisphosphate (IP3) is thought to be a second messenger for intracellular calcium mobilization. However, in cell-free system of islet microsomes, cyclic adenosine diphosphate-ribose (cADP-ribose), nicotinamide adenine dinucleotide (NAD+) metabolite, but not IP3, induced release. In digitonin-permeabilized islets, cADP-ribose and calcium, insulin secretion. Islet microsomes released when combined with the extract from intact islets that had been incubated high concentrations...
Cyclic ADP-ribose (cADPR) has been recently shown to be generated in pancreatic beta-cells by glucose stimulation, serving as a second messenger for Ca2+ mobilization the endoplasmic reticulum process of insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In present study, we isolated cDNA CD38, which reported human leukocyte antigen, from insulinoma expressed COS-7 cells. CD38 expression was observed plasma membrane microsome fractions When...
Diabetic nephropathy is a major microvascular complication in long-standing diabetic patients who eventually undergo renal dialysis or transplantation. To prevent development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. In study, we examined whether inhibition receptor for glycation end products (RAGE) could attenuate changes kidney. Here, show that inactivation RAGE gene mouse model results significant...
Background —In the pathogenesis of cardiac dysfunction in heart failure, a decrease activity sarcoplasmic reticulum (SR) Ca 2+ -ATPase is believed to be major determinant. Here, we report novel mechanism revealed by assessing functional interaction FK506–binding protein (FKBP12.6) with ryanodine receptor (RyR) canine model pacing-induced failure. Methods and Results —SR vesicles were isolated from left ventricular muscles (normal failure). The stoichiometry FKBP12.6 per RyR was significantly...
Increases in [Ca2+]i pancreatic beta cells, resulting from Ca2+ mobilization intracellular stores as well influx extracellular sources, are important insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated cells glucose stimulation, has been postulated to serve a second messenger for secretion, and CD38 is thought be involved the cADPR accumulation (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, Yonekura, H., Okamoto, H. (1993) J. Biol. Chem. 268,...
Cyclic ADP-ribose (cADPR) is a second messenger for Ca2+ mobilization via the ryanodine receptor (RyR) from islet microsomes insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In present study, FK506, an immunosuppressant that prolongs allograft survival, as well cADPR were found to induce release of microsomes. After treated with by was reduced. FK506 bound FK506-binding protein 12.6 (FKBP12.6), which we also occurs naturally in When...
Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays role in immune reactions recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, bioactive component of cell walls, and RAGE unclear. In this study, we found direct LPS binding by surface plasmon resonance assay, plate competition flow cytometry. increased TNF-α secretion from peritoneal macrophages an NF-κB...
<i>Reg</i> (regeneratinggene) was isolated as a gene specifically expressed in regenerating islets (Terazono, K., Yamamoto, H., Takasawa, S., Shiga, Yonemura, Y., Tochino, and Okamoto, H. (1988) <i>J. Biol. Chem.</i> 263, 2111–2114). Rat human products, Reg/REG proteins, have been demonstrated to stimulate islet β-cell growth <i>in vitro</i> vivo</i> ameliorate experimental diabetes. In the present study, we cDNA for Reg protein receptor from rat library. The encoded cell surface 919-amino...
Human BST‐1, a bone marrow stromal cell surface molecule, is GPI‐anchored protein that facilitates the growth of pre‐B cells. The deduced amino acid sequences human and mouse BST‐1 show around 30% homology with those CD38 Aplysia ADP ribosyl cyclase. Therefore, like CD38, might possess cyclase activity. Here, we report establishment stable transformant CHO line which secretes truncated soluble purified displays both cADPR hydrolase activities.
Although microorganisms play a role in gut inflammation, it remains uncertain which epithelial genes are expressed response to luminal flora and whether these molecules also involved pathologic mucosal inflammation. Germ-free mice were orally challenged with bacterial suspension prepared from conventionally housed (bacterial reconstitution). Thereafter, the differential gene expression cells was identified by display. The of examined dextran sulfate sodium (DSS)-induced colitis human...
We generated transgenic mice carrying the mouse type 2 nitric-oxide synthase (NOS2) cDNA under control of insulin promoter. Western and immunohistochemical analyses revealed that NOS2 was expressed abundantly in islets but not islets. When were isolated cultured, high levels nitrite released from In mice, beta cell mass markedly reduced without infiltration macrophages or lymphocytes, extensive DNA strand breaks detected by situ nick translation. All developed hypoinsulinemic diabetes 4...
Intracellular Ca<sup>2+</sup> mobilization occurs in a variety of cellular processes and is mediated by two major systems, the inositol 1,4,5-trisphosphate (IP<sub>3</sub>) cyclic ADP-ribose (cADPR) systems. cADPR has been proposed to be second messenger for insulin secretion induced glucose pancreatic β-cells (Takasawa, S., Nata, K., Yonekura, H., Okamoto, H. (1993)<i>Science</i> 259, 370–373). Here we show that signal system replaced IP<sub>3</sub> diabetic such as <i>ob/ob</i> mouse...
Glucagon-like peptide-1 (GLP-1) increases intracellular Ca(2+) concentrations ([Ca(2+)](i)), resulting in insulin secretion from pancreatic beta-cells. The molecular mechanism(s) of the GLP-1-mediated regulation [Ca(2+)](i) was investigated.GLP-1-induced changes were measured beta-cells isolated Cd38(+/+) and Cd38(-/-) mice. Calcium-mobilizing second messengers identified by measuring levels nicotinic acid adenine dinucleotide phosphate (NAADP) cyclic ADP-ribose (ADPR), using a enzymatic...
Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated vitro and vivo that the exogenous addition of rat human products, Reg/REG proteins, induced β-cell replication via receptor thereby ameliorated experimental diabetes. In present study, we produced knockout mice by homologous recombination. The disruption resulted null mutation. Knockout developed normally. Islets from appeared morphologically indistinguishable those normal...
serves as a second messenger for glucoseinduced insulin secretion (Takasawa, S.,