A5041827294- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Peptidase Inhibition and Analysis
- Chronic Kidney Disease and Diabetes
- Phagocytosis and Immune Regulation
- Estrogen and related hormone effects
- Extracellular vesicles in disease
- Genetic and Kidney Cyst Diseases
- Biomedical Research and Pathophysiology
- Biomarkers in Disease Mechanisms
- Pancreatic function and diabetes
- Neuroendocrine Tumor Research Advances
- Adenosine and Purinergic Signaling
- Advanced Breast Cancer Therapies
- Renal and related cancers
- Inflammatory mediators and NSAID effects
- Signaling Pathways in Disease
- Neuropeptides and Animal Physiology
- Renal Diseases and Glomerulopathies
- Vitamin D Research Studies
- Vascular anomalies and interventions
- Liver physiology and pathology
- Cardiac Arrhythmias and Treatments
- Abdominal vascular conditions and treatments
- Dialysis and Renal Disease Management
Kanazawa Medical University
2016-2023
National Institute of Biomedical Innovation, Health and Nutrition
2017
Sodium glucose cotransporter 2 (SGLT2) inhibitors are beneficial in halting diabetic kidney disease; however, the complete mechanisms have not yet been elucidated. The epithelial-mesenchymal transition (EMT) is associated with suppression of sirtuin 3 (Sirt3) and aberrant glycolysis. Here, we hypothesized that SGLT2 inhibitor empagliflozin restores normal histology function association inhibition glycolysis kidneys. CD-1 mice streptozotocin-induced diabetes displayed fibrosis was EMT at 4...
Complete mechanisms of renoprotective effects sodium-glucose cotransporter 2 (SGLT2) inhibitors have not been elucidated yet. Mitochondrial biogenesis is regulated by membrane GTPases, such as optic atrophy factor 1 and mitofusion 2. Here, we investigated whether SGLT2 inhibition in mice fed with a high-fat diet (HFD) improved mitochondrial morphology restored biogenesis-related molecules.Mice were control or HFD without ipragliflozin treatment. After 16 weeks, the kidneys taken out utilized...
Dipeptidyl peptidase (DPP)-4 is a multifunctional glycoprotein involved in various biological and pathologic processes. DPP-4 has been widely recognized as therapeutic target for type 2 diabetes mellitus but also implicated the development of human malignancies. Here, we show that inhibition accelerates breast cancer metastasis via induction CXCL12/CXCR4, which activates mTOR to promote epithelial-mesenchymal transition (EMT). In cultured cells, knockdown induced EMT cell migration....
Macroautophagy/autophagy plays a vital role in the homeostasis of diverse cell types. Vascular endothelial cells contribute to vascular health and play unique biology. Here, we demonstrated that autophagy defects induced IL6 (interleukin 6)-dependent endothelial-to-mesenchymal transition (EndMT) organ fibrosis with metabolic mice. Inhibition autophagy, either by specific inhibitor or small interfering RNA (siRNA) for ATG5 (autophagy related 5), human microvascular (HMVECs) EndMT. The level...
Defects in endothelial cells cause deterioration kidney function and structure. Here, we found that SIRT3 regulates metabolic reprogramming fibrogenesis the kidneys of diabetic mice. By analyzing, gain gene by overexpression a fibrotic mouse strain conferred disease resistance against fibrosis, whereas its loss exacerbated levels fibrosis. Regulation cell on fibrogenic processes was due to tight control over defective central metabolism linked activation endothelial-to-mesenchymal transition...
Abstract Aims/Introduction Tubulointerstitial fibrosis is a hallmark of diabetic nephropathy and associated with an epithelial‐to‐mesenchymal transition (EMT) program aberrant glycolysis. Dimeric pyruvate kinase (PK) M2 (PKM2) acts as key protein in glycolysis by promoting the accumulation hypoxia‐inducible factor (HIF)‐1α, while tetrameric PKM2 functions oxidative phosphorylation. The aim research to study effect tetramer activation on preventing kidney via suppression EMT program....
The biological influence of antidiabetic drugs on cancer cells and diabetic patients has not yet been completely elucidated. We reported that a dipeptidyl peptidase (DPP)-4 inhibitor accelerates mammary metastasis by inducing epithelial-mesenchymal transition (EMT) through the CXCL12/CXCR4/mTOR axis. Metformin shown to inhibit mTOR signaling pathway. In this study, we investigated whether metformin mitigates breast induced DPP-4 via suppression signaling. cultured mouse human cells,...
The role of cell-specific ANGPTL4 is not well known in the context ECs, specifically pathological angiogenesis and its relation to diabetic kidney disease. Here, we demonstrate that endothelial required induce a metabolic phenotype favors mesenchymal activation ECs tubules conditions. Diabetes accelerates fibrogenesis control mice however, same effects were observed endothelial-cell specific knock out mice. This diabetes directly linked with neovascularization, leakage, lipid glycolysis...
Abstract Diabetic kidney disease (DKD) is appeared to be higher risk of declining function compared non-diabetic with same magnitude albuminuria. Epithelial-mesenchymal transition (EMT) program tubular epithelial cells (TECs) could important for the production extracellular matrix in kidney. Caveolin-1 (CAV1), dipeptidyl peptidase-4 (DPP-4) and integrin β1 have shown involved EMT program. Here, we found diabetic prone albuminuria-induced TECs damage DPP-4 plays a vital role such parenchymal...
Abstract Aims/Introduction The aim of this study was to elucidate whether sodium–glucose cotransporter 2 inhibitors (SGLT2is) treatment has any renoprotective effect for type diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m in clinical practice. Materials and Methods We evaluated the annual eGFR slope 85 renal impairment, treated SGLT2is ≥2 years. Each patient's at start therapy. calculation change each patient obtained by acquired data...
Autophagy plays a complex role in breast cancer cell survival, metastasis, and chemotherapeutic resistance. Dipeptidyl peptidase (DPP)-4, therapeutic target for type 2 diabetes mellitus, is also involved autophagic flux. The potential influence of DPP-4 suppression on biology remains unknown. Here, we report that deficiency promotes survival via the induction autophagy by C-X-C motif chemokine 12 (CXCL12)/C-X-C receptor 4 (CXCR4)/mammalian rapamycin (mTOR)/hypoxia inducible factor (HIF)-1α...
To establish novel therapies to combat diabetic kidney disease, a human disease-relevant animal model is essential. However, type 2 mouse presenting progressive fibrosis has not yet been established. Kidneys of streptozotocin-induced CD-1 mice showed severe compared with other backgrounds associated the suppression antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline. The BKS background (BKSdb/db ) often utilized for disease research; in BKSdb/db phenotype minimal.We generated...
Abstract A 58‐year‐old women who was diagnosed with type 2 diabetes 20 years earlier had been treated antidiabetic medicines since she aged 40 years. After sodium–glucose cotransporter inhibitors administration, her bodyweight rapidly decreased from to 30 kg over a period of 3 weeks. She abdominal symptoms, including nausea, especially after meal. On admission, physical examinations and laboratory data showed euglycemic ketoacidosis, dehydration low insulin secretion levels. Additionally,...
Key Clinical Message Vitamin D plays vital role for the health, and its deficiency has been implicated in diverse pathological conditions such as hypomagnesemia abnormal immune system. Here, we present a case of severe electrolytes disorders (hypokalemia etc.) kidney damages associated with vitamin deficiency.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to display excellent renoprotective effects in diabetic kidney disease with macroalbuminuria/proteinuria. Regarding the mechanism of SGLT2i, a sophisticated hypothesis was made by explaining suppression glomerular hypertension/hyperfiltration through adenosine/adenosine type 1 receptor (A1R) signaling-mediated restoration tubuloglomerular feedback mechanism; however, how such A1R signaling is relevant for renoprotection...
<p>Fig. S1 Gene expression profile analysis of primary mammary tumors in control, KR- and KR plus AMD-treated mice. Fig. S2 4T1 cells were treated with (50 μM) and/or metformin (10 mM) cultured for 48 h. S3 h.</p>
<p>Fig. S1 Gene expression profile analysis of primary mammary tumors in control, KR- and KR plus AMD-treated mice. Fig. S2 4T1 cells were treated with (50 μM) and/or metformin (10 mM) cultured for 48 h. S3 h.</p>
<div>Abstract<p>The biological influence of antidiabetic drugs on cancer cells and diabetic patients has not yet been completely elucidated. We reported that a dipeptidyl peptidase (DPP)-4 inhibitor accelerates mammary metastasis by inducing epithelial–mesenchymal transition (EMT) through the CXCL12/CXCR4/mTOR axis. Metformin shown to inhibit mTOR signaling pathway. In this study, we investigated whether metformin mitigates breast induced DPP-4 via suppression signaling. cultured...
<div>Abstract<p>The biological influence of antidiabetic drugs on cancer cells and diabetic patients has not yet been completely elucidated. We reported that a dipeptidyl peptidase (DPP)-4 inhibitor accelerates mammary metastasis by inducing epithelial–mesenchymal transition (EMT) through the CXCL12/CXCR4/mTOR axis. Metformin shown to inhibit mTOR signaling pathway. In this study, we investigated whether metformin mitigates breast induced DPP-4 via suppression signaling. cultured...
Background: Liver fibrosis is characterized by excessive accumulation of extracellular matrix.In a mouse model liver fibrosis, systemic injection Adipose tissuederived multi-lineage progenitor cells (ADMPCs) was considered to rescue the diseased phenotype. Objective:The aim this study assess efficiency ADMPC-cell-sheets on improving fibrosis.Method and results: ADMPCs were isolated from rat inguinal adipose tissues expanded.Production fibrinolytic enzymes MMPs examined ELISA compared that...
Background: In diabetic patients, the incident of heart failure is two to five times greater when compared that general population. The influence DPP-4 inhibitor on and cardiac damage in diabetes not completely elucidated yet. Therefore, understand pathobiology emerged as significant. Necroptosis, recently identified programmed cell death, had shown be involved ischemic disease model. Here we found intervention with linagliptin (LINA) ameliorated mice associated suppression necroptosis....
Background: SGLT2 inhibitor (SGLT2i) displayed remarkable and early renal protection in overt nephropathy cases clinical trials. However, detailed molecular mechanisms by which SGLT2i ameliorated damage proteinuric diabetic patients were not elucidated yet. Here, we investigated that exerted protective effects via adenosine signal mice with proteinuria. Methods: STZ (200mg/kgBW) was injected intraperitoneally to induce diabetes 8-week-old CD-1 mice. Four weeks later, treated intraperitoneal...
Background: The sodium glucose co-transporter 2(SGLT2) inhibitors are beneficial in halting diabetic kidney disease, however complete mechanisms not elucidated yet. Epithelial to mesenchymal transition (EMT) program has been associated with suppression of sirtuin 3 (Sirt3) and aberrant glycolysis. Here, we hypothesized that SGLT2 inhibitor empagliflozin restored normal histology function, the inhibition glycolysis kidney. Methods: In vivo, streptozotocin-induced CD-1 mice, model exhibiting...