Altered expression and localization of insulin receptor in proximal tubule cells from human and rat diabetic kidney
| Autor: | Carme Caelles, Rodrigo Gatica, Alejandro J. Yáñez, Pamela Silva, Romina Bertinat, Juan C. Slebe, Daniel Carpio, Jose María Campistol, María José Ramírez, Rody San Martín, Francisco Nualart |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Kidney Cortex Renal cortex Gene Expression Biochemistry End stage renal disease Kidney Tubules Proximal Rats Sprague-Dawley Diabetic nephropathy Glycogen Synthase Kinase 3 Internal medicine Diabetes mellitus medicine Animals Humans Insulin Diabetic Nephropathies Molecular Biology Aged Kidney Glycogen Synthase Kinase 3 beta biology Cell Biology Apical membrane medicine.disease Receptor Insulin Rats Enzyme Activation Insulin receptor Diabetes Mellitus Type 1 medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 biology.protein Female Phosphoenolpyruvate carboxykinase Phosphoenolpyruvate Carboxykinase (ATP) Signal Transduction |
| Zdroj: | JOURNAL OF CELLULAR BIOCHEMISTRY Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 0730-2312 |
| Popis: | Diabetes is the major cause of end stage renal disease, and tubular alterations are now considered to participate in the development and progression of diabetic nephropathy (DN). Here, we report for the first time that expression of the insulin receptor (IR) in human kidney is altered during diabetes. We detected a strong expression in proximal and distal tubules from human renal cortex, and a significant reduction in type 2 diabetic patients. Moreover, isolated proximal tubules from type 1 diabetic rat kidney showed a similar response, supporting its use as an excellent model for in vitro study of human DN. IR protein down-regulation was paralleled in proximal and distal tubules from diabetic rats, but prominent in proximal tubules from diabetic patients. A target of renal insulin signaling, the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK), showed increased expression and activity, and localization in compartments near the apical membrane of proximal tubules, which was correlated with activation of the GSK3β kinase in this specific renal structure in the diabetic condition. Thus, expression of IR protein in proximal tubules from type 1 and type 2 diabetic kidney indicates that this is a common regulatory mechanism which is altered in DN, triggering enhanced gluconeogenesis regardless the etiology of the disease. |
| Databáze: | OpenAIRE |
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