Gliquidone decreases urinary protein by promoting tubular reabsorption in diabetic Goto-Kakizaki rats
| Autor: | Li Chen, Yong-Wei Jiang, Wenjian Zhang, Jin-Ning Lou, Shiqing Xu, M i Li, Jian-Ting Ke, Lan-yun Cheng, Wei Wu |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Drug Evaluation Preclinical urologic and male genital diseases Absorption Diabetes Mellitus Experimental Podocyte Diabetic nephropathy Endocrinology Glycation Internal medicine medicine Animals Humans Hypoglycemic Agents Diabetic Nephropathies Cells Cultured Chemistry Glomerular basement membrane Albumin Rats Inbred Strains medicine.disease Cubilin Rats Proteinuria Kidney Tubules Sulfonylurea Compounds medicine.anatomical_structure Renal physiology Gliquidone medicine.drug |
| Zdroj: | Journal of Endocrinology. 220:129-141 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1530/joe-13-0199 |
| Popis: | The efficacy of gliquidone for the treatment of diabetic nephropathy was investigated by implanting micro-osmotic pumps containing gliquidone into the abdominal cavities of Goto-Kakizaki (GK) rats with diabetic nephropathy. Blood glucose, 24 h urinary protein, and 24 h urinary albumin levels were measured weekly. After 4 weeks of gliquidone therapy, pathological changes in the glomerular basement membrane (GBM) were examined using an electron microscope. Real-time PCR, western blotting, and immunohistochemistry were employed to detect glomerular expression of receptors for advanced glycation end products (RAGE) (AGER), protein kinase C β (PKCβ), and protein kinase A (PKA) as well as tubular expression of the albumin reabsorption-associated proteins: megalin and cubilin. Human proximal tubular epithelial cells (HK-2 cells) were used to analyze the effects of gliquidone and advanced glycation end products (AGEs) on the expression of megalin and cubilin and on the absorption of albumin. Gliquidone lowered blood glucose, 24 h urinary protein, and 24 h urinary albumin levels in GK rats with diabetic nephropathy. The level of plasma C-peptide increased markedly and GBM and podocyte lesions improved dramatically after gliquidone treatment. Glomerular expression of RAGE and PKCβ decreased after gliquidone treatment, while PKA expression increased. AGEs markedly suppressed the expression of megalin and cubulin and the absorption of albumin in HK-2 cells in vitro, whereas the expression of megalin and cubilin and the absorption of albumin were all increased in these cells after gliquidone treatment. In conclusion, gliquidone treatment effectively reduced urinary protein in GK rats with diabetic nephropathy by improving glomerular lesions and promoting tubular reabsorption. |
| Databáze: | OpenAIRE |
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