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Glomerular and Tubular Function in the Diabetic Kidney

糖尿病肾的肾小球和肾小管功能

基本信息

批准号：
9384689
负责人：
SCOTT Culver THOMSON
金额：
$ 43.85万
依托单位：
VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9384689
关键词：
5&apos -AMP-activated protein kinase Address Affect Agonist Antidiabetic Drugs Blood Glucose Blood Pressure Caring Clinical Clinical Trials Coupling Diabetes Mellitus Diet Electron Transport Elements Equilibrium Fibrosis GLP-I receptor Glomerular Capillary Gluconeogenesis Glucose Goals Growth Homeostasis Hypersensitivity Hypertension Hypoxia Kidney Knowledge Logic Measures Mediating Medical Metabolic Metabolic stress Metabolism Metformin Methods Micropuncture Modeling Mus Nephrons Organ Outcome Oxygen Oxygen Consumption Patients Pharmaceutical Preparations Physiology Public Health Rattus Receptor Activation Recommendation Renal Blood Flow Renal function Research Role Series Systems Theory Testing Time Tissues Tubular formation Work diabetic diabetic patient dietary salt exenatide experimental study glomerular filtration hemodynamics in vivo inhibitor/antagonist insight mitochondrial dysfunction pressure protective effect renal hypoxia response saluretic treatment effect

项目摘要

PROJECT SUMMARY ABSTRACT The kidney is unique among the body organs in that it responds to early diabetes by growing large and increasing its function and oxygen consumption (QO2). We are drawn to understand this physiology because growth, hyperfunction, and low cortical PO2 in the early diabetic kidney predict subsequent damage and decline. For the past 15 years, we have characterized glomerular and tubular function in the early diabetic kidney with particular emphasis on how glomerular filtration and proximal reabsorption affect each other. This application is focused on the renal effects of dietary salt and of common drugs that are already in the armamentarium of diabetes care. These drugs include inhibitors of the Na-glucose cotransporter SGLT2 and agonists of the glucagon-like peptide 1 receptor (GLP-1R). SGLT2 inhibitors and GLP-1R agonists are being administered to millions of diabetic patients, and lowering of the dietary salt would apply to millions more if public health recommendations were successfully implemented. Each of these maneuvers has off-target effects on glomerular and tubular function, the nuances of which we intend to investigate. The goal is to facilitate the acquisition of medical knowledge by providing a basis in physiology for developing hypotheses that are worth bringing to clinical trials for renal protection and for providing a scientific explanation of the outcome of such trials that are already in progress. The experimental work is divided into 3 Specific Aims. Each aim addresses the impact of dietary salt, SGLT2 blockade, and GLP-1R activation on a particular aspect of kidney physiology. The three aspects of kidney physiology are 1) proximal tubular growth and transport, 2) renal hemodynamics, and 3) renal metabolism. A network assembled from cause-effect relations among transport, hemodynamic, and metabolic variables provides insight to the organic physiology that could not be determined by studying transport, hemodynamics, and metabolism in isolation.

项目摘要