A5088962666- Diabetes Treatment and Management
- Chronic Kidney Disease and Diabetes
- Advanced Glycation End Products research
- Renal Diseases and Glomerulopathies
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Peroxisome Proliferator-Activated Receptors
- Nitric Oxide and Endothelin Effects
- Diabetes and associated disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Erythropoietin and Anemia Treatment
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Alcohol Consumption and Health Effects
- Pancreatic function and diabetes
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Ion Transport and Channel Regulation
- Genetic and Kidney Cyst Diseases
- Connective Tissue Growth Factor Research
- Biosimilars and Bioanalytical Methods
- Adenosine and Purinergic Signaling
- Cardiovascular Function and Risk Factors
- Genetic Syndromes and Imprinting
- Neurological Disorders and Treatments
The University of Sydney
2010-2020
Royal North Shore Hospital
2010-2020
RELX Group (United States)
2018
High-mobility group box 1 (HMGB1), a nuclear factor released extracellularly as an inflammatory cytokine, is endogenous ligand for Toll-like receptor 4 (TLR4). TLR4 activation mediates kidney ischemia-reperfusion injury (IRI), but whether HMGB1 contributes to IRI unknown. Here, treating wild-type mice with neutralizing anti-HMGB1 antibody protected them against IRI, evidenced by lower serum creatinine and less tubular damage than untreated mice. Mice treated had significantly...
Sodium/glucose cotransporter 2 (SGLT2) inhibitors are oral hypoglycemic agents used to treat patients with diabetes mellitus. SGLT2 block reabsorption of filtered glucose by inhibiting SGLT2, the primary transporter in proximal tubular cell (PTC), leading glycosuria and lowering serum glucose. We examined renoprotective effects inhibitor empagliflozin determine whether blocking entry into kidney PTCs reduced inflammatory fibrotic responses high an vitro model human PTCs. HK2 cells (human PTC...
Toll like receptor (TLR) 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 complicated pathophysiology nephropathy is not understood. In this study, we report elevated expression TLR4, its endogenous ligands and downstream cytokines, chemokines fibrogenic genes WT mice with streptozotocin (STZ) diabetes. Subsequently, demonstrated that TLR4−/− were protected against development nephropathy, exhibiting less albuminuria, inflammation, glomerular...
Abstract Blood glucose control is the primary strategy to prevent complications in diabetes. At onset of kidney disease, therapies that inhibit components renin angiotensin system (RAS) are also indicated, but these approaches not wholly effective. Here, we show once daily administration novel lowering agent, empagliflozin, an SGLT2 inhibitor which targets block reabsorption, has potential improve disease type 2 In male db / mice, a 10-week treatment with empagliflozin attenuated...
Inflammatory responses are central to the pathogenesis of diabetic nephropathy. Toll-like receptors (TLRs) ligand-activated membrane-bound which induce inflammatory predominantly through activation NF-κB. TLR2 and 4 present in proximal tubular cells activated by endogenous ligands upregulated nephropathy, including high-mobility group box-1 (HMGB1) fibronectin. Human tubules were exposed 5 mM (control), 11.2 (approximating clinical diagnostic threshold for diabetes mellitus), 30 (high)...
Postprandial hyperglycemia induces inflammation and endothelial dysfunction resulting in vascular complications patients with diabetes. Toll-like receptors (TLRs) are central to the regulation of inflammatory responses through activation nuclear factor-kappa B (NF-ĸB). This study examined role TLR2 4 regulating when exposed fluctuating glucose concentrations. HMEC-1 cells (a human microvascular cell line) were control (5 mM), 30 mM (high), (5/30 mM) 11.2 (approximate glycaemic criteria for...
Peroxisome proliferator-activated receptor-gamma (PPARgamma) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity. We recently demonstrated PPARgamma agonists limit high glucose-induced inflammation in a model of proximal tubular cells (PTC; Panchapakesan U, Pollock CA, Chen XM. Am J Physiol Renal 287: F528-F534, 2004). However, the role excess extracellular matrix production is largely unknown. evaluated effect 24- to...
Abstract Aim In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown be antifibrotic and anti‐inflammatory. We previously that DPP4 inhibition human kidney proximal tubular cells exposed high reduced fibrotic inflammatory markers. Hence, we wanted demonstrate renoprotection an vivo model. Methods used a 1 diabetic animal model explore the renoprotective potential of saxagliptin independent lowering. induced...
Background and Objective Sodium glucose cotransporter 2 (SGLT2) is the main luminal transporter in kidney. SGLT2 inhibition results glycosuria improved glycaemic control. Drugs inhibiting this have recently been approved for clinical use suggested to potential renoprotective benefits by limiting glycotoxicity proximal tubule. We aimed determine of empagliflozin, an inhibitor, independent its lowering effect. Research Design Methods induced diabetes using a low dose streptozotocin protocol...
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity. PPAR-gamma in the human kidney has been described. However, role of proximal tubular cells with respect to growth inflammation diabetic nephropathy is largely unknown. We evaluated effect high (30 mM) D-glucose, thiazolidinedione pioglitazone (10 microM), selective agonist L-805645 (8 microM) on...
Background In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown be antifibrotic. We previously that cation independent mannose-6-phosphate receptor (CIM6PR) facilitates the conversion of latent active transforming growth factor β1 (GFß1) renal proximal tubular cells (PTCs) and linagliptin (a DPP4 inhibitor) reduced this downstream reduction fibronectin transcription. Objective wanted demonstrate reduces high...
Hyperglycemia and hypoxia have independent convergent roles in the development of renal disease. Transforming growth factor-β 1 (TGF-β ) is a key cytokine promoting production extracellular matrix proteins. The cationic-independent mannose 6-phosphate receptor (CI-M6PR) membrane protein that binds M6P-containing A role to activate latent TGF-β . PXS25, novel CI-MPR inhibitor, has antifibrotic properties skin fibroblasts, but its fibrosis unclear. aim was study PXS25 under high glucose ±...
The aim of the study was to investigate effect DPP-4 inhibitor linagliptin on mechanism(s) endothelium-dependent relaxation in mesenteric arteries from STZ-induced diabetic rats. Both normal and animals received (2 mg/kg) daily by oral gavage for a period 4 weeks. To measure superoxide generation arteries, lucigenin-enhanced chemiluminescence used. ACh-induced assessed using organ bath techniques Western blotting used protein expression. Pharmacological tools (1 μM TRAM-34, 1 apamin, 100 nM...