Open Library Archives of Kagawa University (OLIVE)
Not a member yet
10866 research outputs found
Sort by
Potential for Premium Mass Marketing : A Case Study of Ishimaru Seimen
Get PDFdepartmental bulletin pape
NMDA Suppresses Pancreatic ABCA1 Expression through the MEK/ERK/LXR Pathway in Pancreatic Beta Cells
Get PDF香川大学Kagawa University博士（医学）Dysfunction or loss of pancreatic β cells can cause insulin deficiency and impaired glucose regulation, resulting in conditions like type 2 diabetes. The ATP-binding cassette transporter A1 (ABCA1) plays a key role in the reverse cholesterol transport system, and its decreased expression is associated with pancreatic β cell lipotoxicity, resulting in abnormal insulin synthesis and secretion. Increased glutamate release can cause glucotoxicity in β cells, though the detailed mechanisms remain unclear. This study investigated the effect of N-methyl-D-aspartic acid (NMDA) on ABCA1 expression in INS-1 cells and primary pancreatic islets to elucidate the signaling mechanisms that suppress insulin secretion. Using Western blotting, microscopy, and biochemical analyses, we found that NMDA activated the mitogen-activated protein kinase (MEK)-dependent pathway, suppressing ABCA1 protein and mRNA expression. The MEK-specific inhibitor PD98059 restored ABCA1 promoter activity, indicating the involvement of the extracellular signal-regulated kinase (MEK/ERK) pathway. Furthermore, we identified the liver X receptor (LXR) as an effector transcription factor in NMDA regulation of ABCA1 transcription. NMDA treatment increased cholesterol and triglyceride levels while decreasing insulin secretion, even under high-glucose conditions. These effects were abrogated by treatment with PD98059. This study reveals that NMDA suppresses ABCA1 expression via the MEK/ERK/LXR pathway, providing new insights into the pathological suppression of insulin secretion in pancreatic β cells and emphasizing the importance of investigating the role of NMDA in β cell dysfunction.doctoral thesi
Therapeutic effect of proteinase-activated receptor-1 antagonist on colitis-associated carcinogenesis
No full textプロテイナーゼ活性化型受容体1（PAR1）拮抗薬E5555による腸炎関連発癌の改善効果を明らかにした。E5555は炎症・線維化・発癌の改善効果のみならず、腸内細菌にも影響及ぼし、炎症性発癌の新規治療戦略として提案したい。Background & Aims
Inflammatory bowel disease is associated with carcinogenesis, which limits the prognosis of the patients. The local expression of proteinases and proteinase-activated receptor 1 (PAR1) increases in inflammatory bowel disease. The present study investigated the therapeutic effects of PAR1 antagonism on colitis-associated carcinogenesis.Methods
A colitis-associated carcinogenesis model was prepared in mice by treatment with azoxymethane (AOM) and dextran sulfate sodium (DSS). PAR1 antagonist E5555 was administered in long- and short-term protocol, starting on the day of AOM injection and 1 week after completing AOM/DSS treatment, respectively. The fecal samples were collected for metagenome analysis of gut microbiota. The intestinal myofibroblasts of the Crohn’s disease patients were used to elucidate underlying cellular mechanisms. Caco-2 cells were used to investigate a possible source of PAR1 agonist proteinases.Results
AOM/DSS model showed weight loss, diarrhea, tumor development, inflammation, fibrosis, and increased production of inflammatory cytokines. The β-diversity, but not α-diversity, of microbiota significantly differed between AOM/DSS and control mice. E5555 alleviated these pathological changes and altered the microbiota β-diversity in AOM/DSS mice. The thrombin expression was up-regulated in tumor and non-tumor areas, whereas PAR1 mRNA expression was higher in tumor areas compared with non-tumor areas. E5555 inhibited thrombin-triggered elevation of cytosolic Ca2+ concentration and ERK1/2 phosphorylation, as well as IL6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in intestinal myofibroblasts. Caco-2 cell-conditioned medium contained immunoreactive thrombin, which cleaved the recombinant protein containing the extracellular domain of PAR1 at the thrombin cleavage site.journal articl
Insect observation records mainly from light traps in the vicinity of Nagasaki-no hana (Yashima), in the eastern part of Takamatsu City, Kagawa Prefecture
Get PDFNagasaki-no-hana is a cape jutting out into the Seto Inland Sea at the northern tip of the Yashima peninsula in Takamatsu city, Kagawa prefecture, and belongs to Seto Naikai National Park. Insects were observed and recorded over a period of one year from March 2022, mainly by light trapping. A list of 87 species that could be identified is presented. Species for which identification was uncertain were withheld.journal articl
