A5012416308- Signaling Pathways in Disease
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Apelin-related biomedical research
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Toxin Mechanisms and Immunotoxins
- Adipose Tissue and Metabolism
- Diet, Metabolism, and Disease
- Marine Biology and Environmental Chemistry
- Gout, Hyperuricemia, Uric Acid
- Ubiquitin and proteasome pathways
- Gut microbiota and health
- Diabetes Treatment and Management
- Peroxisome Proliferator-Activated Receptors
- Peptidase Inhibition and Analysis
- Lipid metabolism and disorders
- Sirtuins and Resveratrol in Medicine
- Alcohol Consumption and Health Effects
- Aldose Reductase and Taurine
- NF-κB Signaling Pathways
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Environmental Toxicology and Ecotoxicology
- Endoplasmic Reticulum Stress and Disease
Hiroshima University
2016-2025
The Institute of Medical Science, Asahi Life Foundation
2011-2013
The University of Tokyo
2011-2013
Tohoku University
2013
RIKEN BioResource Research Center
2013
Boehringer Ingelheim (Japan)
2013
Institute of Molecular Medicine
2012
Insulin resistance with elevated glucose is a risk factor for non-alcoholic steatohepatitis (NASH). We investigated the effects of sodium cotransporter 2 (SGLT2) inhibitor luseogliflozin on NASH development using rodent model.Mice were treated both nicotinamide and streptozotocin (NA/STZ) to reduce insulin secretory capacity, then fed high fat diet containing trans fatty acids (HFDT) 8 weeks. The NA/STZ HFDT-fed mice divided into two groups, either or untreated, during this period....
Gut microbiota alterations are associated with various disorders. In this study, gut changes were investigated in a methionine-choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH) rodent model, and the effects of administering Lactobacillus casei strain Shirota (LcS) on development NASH also investigated. Mice divided into three groups, given normal chow diet (NCD), MCD diet, or plus daily oral administration LcS for 6 wk. analyses groups revealed that lactic acid...
Recent clinical studies have revealed the treatment of diabetic patients with sodium glucose co-transporter2 (SGLT2) inhibitors to reduce incidence cardiovascular events. Using nicotinamide and streptozotocin (NA/STZ) -treated ApoE KO mice, we investigated effects short-term (seven days) SGLT2 inhibitor luseogliflozin on mRNA levels related atherosclerosis in aorta, as well examining long-term (six months) development. Eight-week-old mice were treated NA/STZ induce diabetes mellitus, then...
Insulin-like growth factors (IGFs) induce proliferation of various cell types and play important roles in somatic cancer development. Phosphorylation insulin receptor substrate (IRS)-1/2 by IGF-I tyrosine kinase is essential for IGF action. Here we identify Nedd4 as an IRS-2 ubiquitin ligase. monoubiquitinates IRS-2, which promotes its association with Epsin1, a ubiquitin-binding protein. recruits to the membrane, probably through promoting Epsin1 binding, enhances receptor-induced...
Xanthine oxidase (XO) is an enzyme involved in the production of uric acid (UA) from purine nucleotides. Numerous recent studies have revealed likelihood metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) to be related hyperuricemia. However, it remains unclear whether elevated serum UA during development NAFLD NASH a cause consequence these diseases. In this study, XO inhibitor febuxostat was administered two types model mice. Febuxostat exerted...
Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and low level correlates with risk for metabolic syndrome including diabetes, obesity, cardiovascular events. However, underlying molecular mechanism(s) linking SHBG remains unknown. In this study, using adipocytes macrophages, we focused on in vitro effects of inflammation as well lipid metabolism. Incubation 20 nM markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such MCP-1,...
Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that associates with the pSer/Thr-Pro motif and catalyzes cis-trans isomerization. We identified Pin1 in immunoprecipitates of overexpressed IRS-1 myc FLAG tags mouse livers confirmed association between by not only overexpression experiments but also endogenously liver. The analysis using deletion- point-mutated constructs revealed WW domain located N terminus Ser-434 SAIN (Shc NPXY binding) to be involved...
Dipeptidyl peptidase IV (DPP-IV) expression in visceral adipose tissue is reportedly increased obese patients, suggesting an association of DPP-IV with inflammation. In this study, first, lipopolysaccharide (LPS)- or palmitate-induced elevations inflammatory cytokine mRNA expressions RAW264.7 macrophages were shown to be significantly suppressed by coincubation a inhibitor, anagliptin (10 μM), despite low the cells. Regarding molecular mechanism, LPS-induced degradation IκBα and...
Recently, clinical studies have shown the protective effects of sodium glucose co-transporter2 (SGLT2) inhibitors against progression diabetic nephropathy, but underlying molecular mechanisms remain unclear. Diabetic mice were prepared by injecting nicotinamide and streptozotocin, followed high-sucrose diet feeding (NA/STZ/Suc mice). The SGLT2 inhibitor canagliflozin was administered as a 0.03% (w/w) mixture in for 4 weeks. Then, various parameters on nephropathy investigated. Canagliflozin...
Obesity is characterized by macrophage infiltration into adipose tissue. White tissue remodelling under inflammatory conditions involves both hypertrophy and adipogenesis regulated transcription factors, which are influenced bone morphogenetic protein (BMP) signalling. MicroRNAs (miRNAs) regulate gene expression involved in obesity-related processes such as adipogenesis. Therefore, we identified differentially expressed miRNAs the epididymal white (eWAT) of mice fed a normal diet (ND) those...
Tributyltin chloride (TBT), an endocrine-disrupting chemical, has been used as a heat stabilizer, agricultural pesticide, and component of antifouling paints. In this study, we investigated the concentration dependence mechanisms tributyltin cytotoxicity in PC12 cells. Exposure cells to both 500 nM 2 microM increased number showing nuclear fragmentation, typical apoptotic feature, activated caspase-3. The peak Ca(2+) tributyltin-treated was higher than that intracellular increase induced by...
Carnosic acid (CA), carnosol (CL) and rosmarinic (RA), components of the herb rosemary, reportedly exert favorable metabolic actions. This study showed that both CA CL, but not RA, induce significant phosphorylation AMP-dependent kinase (AMPK) its downstream acetyl-CoA carboxylase 1 (ACC1) in HepG2 hepatoma cells. Glucose-6-phosphatase (G6PC) phosphoenolpyruvate carboxykinase (PCK1), rate-limiting enzymes hepatic gluconeogenesis, are upregulated by forskolin stimulation, this upregulation...
Hyperuricemia has been recognized as a risk factor for insulin resistance well one of the factors leading to diabetic kidney disease (DKD). Since DKD is most common cause end-stage renal disease, we investigated whether febuxostat, xanthine oxidase (XO) inhibitor, exerts protective effect against development DKD. We used KK-Ay mice, an established obese rodent model. Eight-week-old mice were provided drinking water with or without febuxostat (15 μg/mL) 12 weeks and then subjected...
Tributyltin, an endocrine-disrupting chemical, has been used as a heat stabilizer, agricultural pesticide, and component of antifouling paints. In this study, the neurotoxicity tributyltin was investigated in cultured rat cortical neurons. Tributyltin caused marked time- dose-dependent increases number trypan blue–stained cells. Measurement extracellular glutamate concentration showed that release induced by tributyltin. Application receptor antagonists MK-801 CNQX decreased neurotoxicity....
Glucose transporter 1 (GLUT1) is widely distributed throughout various tissues and contributes to insulin-independent basal glucose uptake. Using a split-ubiquitin membrane yeast two-hybrid system, we newly identified 4F2 heavy chain (4F2hc) as protein interacting with GLUT1. Though 4F2hc reportedly forms heterodimeric complexes between amino acid transporters, such LAT1 LAT2, regulates uptake, investigated the effects of on GLUT1 expression associated First, FLAG-tagged hemagglutinin-tagged...
Macrophages are integrated into adipose tissues and interact with adipocytes in obese subjects, thereby exacerbating insulin resistance. This study aimed to elucidate the molecular mechanism underlying insulin-sensitizing effect of angiotensin II receptor blocker (ARB) valsartan, as demonstrated clinical studies. Insulin signaling, i.e., substrate-1 Akt phosphorylations, 3T3-L1 was impaired markedly by treatment tumor necrosis factor-α (TNFα) or culture medium lipopolysaccharide...
Resistin-like molecule (RELM) β is a secretory protein homologous to resistin and reportedly contributes local immune response regulation in gut bronchial epithelial cells. However, we found that activated macrophages also express RELMβ thus investigated the role of development atherosclerosis.It was demonstrated foam cells atherosclerotic lesions human coronary artery abundantly RELMβ. knockout ((-/-)) wild-type mice were mated with apolipoprotein E-deficient background mice. RELMβ(-/-)...
Nonalcoholic steatohepatitis (NASH) is a disorder characterized by simultaneous fat accumulation and chronic inflammation in the liver. In this study, Pin1 expression was revealed to be markedly increased livers of mice with methionine choline-deficient (MCD) diet-induced NASH, rodent model NASH. addition, KO were highly resistant MCD-induced based on series data showing accumulation, inflammation, fibrosis terms Pin1-induced it that levels peroxisome proliferator-activated receptor α its...