A5103135814- Heart Failure Treatment and Management
- Peptidase Inhibition and Analysis
- Cardiac Fibrosis and Remodeling
- Pancreatic function and diabetes
- Genetic Neurodegenerative Diseases
- Heart Rate Variability and Autonomic Control
- Eicosanoids and Hypertension Pharmacology
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Neuropeptides and Animal Physiology
- Asymmetric Hydrogenation and Catalysis
- Neurological and metabolic disorders
- Traditional Chinese Medicine Analysis
- Cardiomyopathy and Myosin Studies
- Nitric Oxide and Endothelin Effects
- Parkinson's Disease Mechanisms and Treatments
- Diabetes and associated disorders
- Protease and Inhibitor Mechanisms
- Prion Diseases and Protein Misfolding
- Cardiovascular Function and Risk Factors
- Pluripotent Stem Cells Research
- Xenotransplantation and immune response
- Neurological diseases and metabolism
- Alcohol Consumption and Health Effects
Takeda (Japan)
2015-2019
Kyoto University
2017
Kyoto University Hospital
2017
Akebono Clinic
2005-2010
The University of Tokyo
2004-2007
Tokyo University of Pharmacy and Life Sciences
1999-2007
National Cerebral and Cardiovascular Center
2000-2004
National Defense Medical College
2003
Tokyo Metropolitan Institute of Gerontology
2003
Kameda Medical Center
2002-2003
Adiponectin/Acrp30 is a hormone secreted by adipocytes, which acts as an antidiabetic and antiatherogenic adipokine. We reported previously that AdipoR1 -R2 serve receptors for adiponectin mediate increased fatty acid oxidation glucose uptake adiponectin. In the present study, we examined expression levels roles of AdipoR1/R2 in several physiological pathophysiological states such fasting/refeeding, obesity, insulin resistance. Here show target organs, skeletal muscle liver, significantly...
We examined the effects of activation peroxisome proliferator–activated receptor (PPAR)α, PPARγ, and both them in combination obese diabetic KKAy mice investigated mechanisms by which they improve insulin sensitivity. PPARα its agonist, Wy-14,643, as well PPARγ rosiglitazone, markedly improved Interestingly, dual -γ a Wy-14,643 rosiglitazone showed increased efficacy. Adipocyte size Wy-14,643–treated was much smaller than that vehicle- or rosiglitazone-treated mice, suggesting prevents...
We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic resistance, lack of compensatory beta cell hyperplasia, and leptin resistance. To more precisely determine the roles Irs2 in cells hypothalamus, we generated cell-specific hypothalamus-specific knockdown (betaHT-IRS2) mice. Expression mRNA was reduced by approximately 90% pancreatic islets markedly arcuate nucleus hypothalamus. By contrast, expression liver, muscle, adipose...
C-type natriuretic peptide (CNP), the third member of family, is known to be synthesized in central nervous system and vascular endothelial cells, contrast atrial brain peptide. However, there have been no studies concerning CNP production cultured cardiac cells. Here, we examined local effect ventricular Under serum-free conditions, adult rat fibroblasts secreted immunoreactive time dependently. TGF-β1, basic fibroblast growth factor, endothelin-1 significantly stimulated secretion....
Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced the plasma of patients with cancer, suggesting that this adipokine may mechanically involved pathogenesis adiposity‐related carcinogenesis. In study, we examined expression adiponectin receptors (AdipoR1 and AdipoR2) assessed function gastric cancer. All six cancer cell lines significantly expressed mRNA protein both variable levels. Addition 30 µg/mL potently induced apoptosis inhibited...
Acyl CoA:monoacylglycerol acyltransferase-2 (MGAT2) has attracted interest as a novel target for the treatment of obesity and metabolic diseases. Starting from N-phenylbenzenesulfonamide derivative 1 with moderate potency MGAT2 inhibition, we explored an effective location hydrophobic group at 1-position to enhance inhibitory activity. Shifting adjacent position followed by introduction bicyclic central core restrict substituent orientation produced N-phenylindoline-5-sulfonamide 10b, which...
Monoacylglycerol O-acyltransferase 2 (MGAT2) catalyzes the synthesis of diacylglycerol (DG), a triacylglycerol precursor and potential peripheral target for novel anti-obesity therapeutics. High-throughput screening identified lead compounds with MGAT2 inhibitory activity. Through structural modification, potent, selective, orally bioavailable inhibitor, compound A (compA), was discovered. CompA dose-dependently inhibited postprandial increases in plasma triglyceride (TG) levels. Metabolic...
Cardiac remodelling is a fundamental response to hypertension, myocardial infarction and chronic heart failure, involves cardiac fibroblast proliferation production of extracellular matrix components such as collagen. The present study was performed examine the role endogenous atrial natriuretic peptide (ANP) possible paracrine factor for fibroblasts, effects three neutral endopeptidase (NEP) inhibitors, thiorphan, phosphoramidon ONO‐BB‐039‐02 (ONO‐BB) on ANP‐induced changes in collagen...
Purpose To determine the characteristic magnetic resonance imaging (MRI) findings of early- and late-stage Machado–Joseph disease (MJD) to examine correlation with pathologic specimens. Patients Methods Four patients genetically diagnosed MJD a familial case were all examined using MRI. was pathologically confirmed in one four patients, compared MRI results. Results In three who had for less than 8 years, mild cerebellar atrophy, particularly vermis, atrophic changes superior peduncle. Mild...
Sampatrilat is a novel vasopeptidase inhibitor that may offer greater benefit than traditional angiotensin-converting enzyme (ACE) inhibitors in the treatment of chronic heart failure (CHF). The present study was undertaken to determine whether sampatrilat improves hemodynamic function and cardiac remodeling through direct action on failing rats with CHF following left coronary artery ligation (CAL). (30 mg/kg day) administered orally animals from 1st 6th week after operation. reduced...
Objective: Increased secretion of atrial and brain natriuretic peptide (ANP BNP) from hearts is known to exhibit favorable effects in patients animals with heart failure, inhibition neutral endopeptidase (NEP), an enzyme that degrades ANP BNP, may further increase these levels. However, it still unknown whether such elevation the BNP offer a therapeutic benefit progression chronic failure (CHF). We examined ONO-9902, novel NEP inhibitor, on changes hemodynamic parameters, activity...
Monoacylglycerol O-acyltransferase 2 (MGAT2) is one of the key enzymes responsible for triglyceride (TG) re-synthesis in small intestine. We have previously demonstrated that pharmacological inhibition MGAT2 has beneficial effects on obesity and metabolic disorders mice. Here, we further investigate (a) fat-induced gut peptide release fat intake normal mice (b) high-fat diet (HFD)-fed ob/ob mice, a model severe type diabetes mellitus, using an orally bioavailable inhibitor Compound B (CpdB)....
In the development of cell therapy products, immunocompromised animal models closer in size to humans are valuable for enhancing translatability vivo findings clinical trials. present study, we generated type 1 diabetic Göttingen mini-pig and demonstrated engraftment human-induced pluripotent stem cell–derived pancreatic islet cells (iPICs). We induced hyperglycemia with a concomitant reduction endogenous C-peptide levels pigs that underwent thymectomy splenectomy. After estimating effective...
1. Inhibition of the renin-angiotensin system (RAS) improves symptoms and prognosis in heart failure. The experimental basis for these benefits remains unclear. We examined effects inhibition ACE or blockade angiotensin II type 1 (AT1) receptor on haemodynamics, cardiac G-proteins, collagen synthesis rats with coronary artery ligation (CAL), a model which chronic failure (CHF) is induced. 2. Rats were orally treated inhibitor trandolapril (3 mg kg(-1) day(-1)) AT1 blocker L-158809 (1 from...
The possible effects of tanshinone VI (tsh), a diterpene from the root Tan-Shen (Salvia miltiorrhiza, Bunge (Labiatae)) on hypertrophy and fibrosis in cultured neonatal rat cardiac myocytes fibroblasts were examined. Tsh had no significant effect protein synthesis, which was evaluated by [3H]-leucine incorporation into acid insoluble fraction cells, absence stimulatory factors myocytes. amount produced increased 10(-8) M endothelin-1 (ET-1), 10(-6) phenylephrine (PE), or insulin-like growth...
We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic resistance, lack of compensatory β cell hyperplasia, and leptin resistance. To more precisely determine the roles Irs2 in cells hypothalamus, we generated cell–specific hypothalamus-specific knockdown (βHT-IRS2) mice. Expression mRNA was reduced by approximately 90% pancreatic islets markedly arcuate nucleus hypothalamus. By contrast, expression liver, muscle, adipose tissue...