A5015476095- Chronic Kidney Disease and Diabetes
- Nitric Oxide and Endothelin Effects
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Hormonal Regulation and Hypertension
- Renal Diseases and Glomerulopathies
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Sirtuins and Resveratrol in Medicine
- Renin-Angiotensin System Studies
- Eicosanoids and Hypertension Pharmacology
- Protein Kinase Regulation and GTPase Signaling
- Blood Pressure and Hypertension Studies
- Genetic and Kidney Cyst Diseases
- Autophagy in Disease and Therapy
- Adenosine and Purinergic Signaling
- Liver Disease Diagnosis and Treatment
- Bacterial Genetics and Biotechnology
- Context-Aware Activity Recognition Systems
- Diet and metabolism studies
- Lipid metabolism and disorders
- Metabolism and Genetic Disorders
- Cancer, Lipids, and Metabolism
- Electrolyte and hormonal disorders
- Dialysis and Renal Disease Management
Shimane University
2023-2025
Keio University
2015-2025
University of Tsukuba
2021-2025
Tokyo Dental College
2023
Tokuyama (Japan)
2023
Tachikawa Hospital
2023
Tokushima University
2023
Tokyo Institute of Technology
2020
Health Center
2012
Brigham and Women's Hospital
2007-2008
Although endothelial dysfunction, defined as abnormal vasoreactivity, is a common early finding in individuals with type 2 diabetes, the endothelium has not been known to regulate metabolism. As PPARγ, transcriptional regulator of energy balance, expressed cells, we set out investigate role cell PPARγ metabolism using mice that lack and BM (γEC/BM-KO). When γEC/BM-KO were fed high-fat diet, they had decreased adiposity increased insulin sensitivity compared control mice, despite serum FFA...
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+-dependent protein deacetylase silent mating type information regulation homolog 1 (Sirtuin-1; SIRT1) PT survival decreases. Therefore, we hypothesized that increased influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine LLC-PK1 cells a two-chamber system were treated the inhibitor...
Ketone bodies including β-hydroxybutyrate (β-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of β-OHB on renal ischemia/reperfusion (IRI). Mice were treated with a continuous infusion using an osmotic mini-pump before and after IRI. also tested effects increasing endogenous serum levels by fasting. Renal IRI was attenuated treatment compared saline control, similar results in fasting condition. reduced number terminal...
Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide S-adenosylhomocysteine. Recently, this enzyme has also been reported modulate hepatic nutrient metabolism, but its role in liver not fully elucidated. We developed transgenic mice overexpressing NNMT elucidate metabolism. When fed a high fat diet containing NAM, precursor for adenine dinucleotide (NAD)
The role of gut microbiota in the progression chronic kidney disease (CKD) has not been fully elucidated.Renal failure was induced 6-week-old spontaneously hypertensive rats by 5/6 nephrectomy (Nx). We analyzed population to identify relevant species potentially involved inducing renal damage. Human colon Caco-2 cells were used delineate mechanism molecular changes Nx rats.Nx showed an increase Bacteroides (Bact) and a decrease Lactobacillus (Lact) compared with sham-operated rats. Lact, but...
Nicotinamide adenine dinucleotide (NAD+) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of NAD+ precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated NMN-producing enzyme phosphoribosyltransferase (Nampt) nephropathy. The expression Nampt PTs was downregulated streptozotocin (STZ)-treated mice when they exhibited This albuminuria ameliorated PT-specific...
The activation of NAD+-dependent deacetylase, Sirt1, by the administration nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases.Diabetic db/db mice were treated with NMN transiently for 2 weeks and observed effects on diabetic nephropathy (DN).At 14 after treatment period, attenuated increases in urinary albumin excretion without ameliorating hemoglobin A1c levels. Short-term mitigated mesangium expansion foot process effacement, while decreased Sirt1 expression...
Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a (NAM) metabolizing enzyme, regulates both NAD + methionine metabolism. Although NNMT is expressed abundantly in kidney, its role CKD renal fibrosis remains unclear. We generated NNMT-deficient mice unilateral ureter obstruction (UUO) model conducted two clinical studies...
Although peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have an antihypertensive effect in vivo, the precise mechanism has not been fully elucidated. We examined their effects on Rho/Rho kinase pathway, a key regulator of vascular tone. In cultured rat aortic smooth muscle cells (RASMC), Rho stimulated by angiotensin II was suppressed pretreatment with pioglitazone and troglitazone, these were explained inhibition translocation to cell membrane. evaluated role Vav,...
Rho-kinase plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of receptor substrate-1 (IRS-1) cultured vascular smooth muscle cells. We therefore examined the development resistance Zucker obese rats. In skeletal muscles aortic tissues rats, activation RhoA/Rho-kinase was observed. Long-term inhibition by 4 wk treatment fasudil (a inhibitor) not only reduced blood pressure but corrected glucose lipid metabolism,...
Dimethylarginie dimethylaminohydrolase (DDAH) is a degrading enzyme for asymmetrical dimethylarginine, an endogenous NO synthase inhibitor. The molecular mechanism DDAH-induced vascular endothelial growth factor (VEGF) expression was examined.Although the transfection of vectors 2 isoforms DDAH, DDAH1, or DDAH2 increased DDAH activity in bovine aortic cells and human umbilical vein cells, secretion VEGF were only DDAH2-transfected cells. Knocking down gene reduced production, overexpression...
Cardiovascular events are accelerated in chronic kidney disease (CKD). Although deranged nitric oxide (NO) pathways and asymmetric dimethylarginine (ADMA) cause endothelial dysfunction, no direct evidence for coronary artery dysfunction CKD has been documented. was induced male dogs by heminephrectomy (1/2Nx) or five-sixths nephrectomy (5/6Nx). After 4 wk, renal ablation reduced GFR (control 76 [54 to 85]; 1/2Nx 38 [29 47]; 5/6Nx 15 [12 46] ml/min) elevated plasma ADMA 1.88 [1.68 2.54]; 2.51...
We explored the renal protective effects by a gut peptide, Ghrelin. Daily peritoneal injection with Ghrelin ameliorated damages in continuously angiotensin II (AngII)-infused C57BL/6 mice as assessed urinary excretion of protein and tubular markers. AngII-induced increase reactive oxygen species (ROS) levels senescent changes were attenuated also inhibited upregulations transforming growth factor-β (TGF-β) plasminogen activator inhibitor-1 (PAI-1), ameliorating fibrotic changes. These...
ABSTRACT Escherichia coli synthesizes aromatic amino acids (AAAs) through the common pathway to produce precursor, chorismate, and three terminal pathways convert chorismate into Phe, Tyr, Trp. E. also imports exogenous AAAs five transporters. GcvB small RNA post-transcriptionally regulates more than 50 genes involved in acid uptake biosynthesis , but full extent of regulon is still underestimated. This study examined all AAA transport using translation reporter assay qRT-PCR analysis. In...
The role of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in glucose metabolism is unknown. Here, we generated DDAH2 transgenic (Tg) mice. These mice had lower plasma levels (60 min: 298±32 vs. 418±35 mg/dl; 120 205±15 284±20 mg/dl) and higher insulin (15 2.1±0.2 1.5±0.1 ng/ml; 30 1.8±0.1 ng/ml) during intraperitoneal tolerance tests when fed a high-fat diet (HFD) compared with HFD-fed wild-type (WT) Glucose-stimulated secretion (GSIS) was increased Tg islets by 33%. Pancreatic...
Highlights•KAT5-mediated DNA damage repair is essential for podocyte maintenance•KAT5 decreased in diabetic nephropathy podocytes•Impaired may be associated with altered methylation status•KAT5 a therapeutic target nephropathySummaryAltered plays an important role the onset and progression of kidney disease. However, little known about how changes arise disease states. Here, we report that KAT5-mediated maintenance podocytes status. Podocyte-specific KAT5-knockout mice develop severe...
We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl elevated arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only 11.6 +/- 0.4 14.1 0.5 microm) but not arterioles 0.2 12.6 0.7 at 10(-5) mol/l. During vasoconstriction Ang Y-27632 restored constriction (141 10% reversal mol/l), whereas ability...