Linagliptin unmasks specific antioxidant pathways protective against albuminuria and kidney hypertrophy in a mouse model of diabetes
Autor: | Jensyn Cone Sullivan, Zhihong Yang, Netanya Y. Spencer, Robert Stanton, Thomas Klein |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Blood Glucose Antioxidant Physiology medicine.medical_treatment lcsh:Medicine Blood Pressure Kidney Biochemistry Antioxidants Mice 0302 clinical medicine Endocrinology Medicine and Health Sciences Diabetic Nephropathies lcsh:Science Glucose-6-Phosphate Dehydrogenase Deficiency Mice Knockout Multidisciplinary biology Anemia Animal Models Hematology Catalase Blood Sugar Enzymes Body Fluids Blood Experimental Organism Systems Physiological Parameters medicine.symptom Anatomy medicine.drug Research Article medicine.medical_specialty Endocrine Disorders Blood sugar 030209 endocrinology & metabolism Mouse Models Linagliptin Glucosephosphate Dehydrogenase Research and Analysis Methods Diabetes Mellitus Experimental 03 medical and health sciences Model Organisms Diabetes mellitus Internal medicine medicine Diabetes Mellitus Albuminuria Animals Hypoglycemic Agents Dipeptidyl-Peptidase IV Inhibitors business.industry Superoxide Dismutase lcsh:R Body Weight Hemolytic Anemia Biology and Life Sciences Proteins Kidneys Renal System medicine.disease Streptozotocin Oxidative Stress 030104 developmental biology Metabolic Disorders biology.protein Enzymology lcsh:Q business Glucose-6-phosphate dehydrogenase deficiency Catalases |
Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 7, p e0200249 (2018) |
ISSN: | 1932-6203 |
Popis: | Background Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects on diabetic kidney disease (DKD) via specific antioxidant pathways. The DPP-4 inhibitor, linagliptin, was evaluated with the hypothesis that DPP-4 inhibition would ameliorate the development of DKD in a glucose-independent manner by altering specific antioxidant function. Methods DBA/2J mice (a well-characterized model of DKD) and glucose 6-phosphate dehydrogenase (G6PD) deficient mice (a model of impaired antioxidant function) were evaluated. Diabetes was induced by streptozotocin. Mice were divided into: diabetic (DM), diabetic+linagliptin (DM+Lina), and non-diabetic control and treated for 12 weeks. Results In DBA/2J mice, there was no difference in body weight and blood glucose between DM and DM+Lina groups. Linagliptin ameliorated albuminuria and kidney hypertrophy in DM DBA/2J mice and specifically increased the mRNA and protein levels for the antioxidants catalase and MnSOD. In G6PD deficient mice, however, increases in these mRNA levels did not occur and linagliptin renoprotection was not observed. Linagliptin also ameliorated histological trends toward mesangial expansion in wild-type mice but not in G6PD deficient mice. Conclusions Linagliptin renoprotection involved glucose-independent but antioxidant-enzyme-system-dependent increases in transcription (not just increased protein levels) of antioxidant proteins in wild-type mice. These studies demonstrate that an intact antioxidant system, in particular including transcription of catalase and MnSOD, is required for the renoprotective effects of linagliptin. |
Databáze: | OpenAIRE |
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