PloS one, 2018-07, Vol.13 (7), p.e0200249-e0200249
2018
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- Autor(en) / Beteiligte
- Titel
- Linagliptin unmasks specific antioxidant pathways protective against albuminuria and kidney hypertrophy in a mouse model of diabetes
- Ist Teil von
- PloS one, 2018-07, Vol.13 (7), p.e0200249-e0200249
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0200249Titel-ID: cdi_plos_journals_2065383781
- Format
- –
- Schlagworte
- Albuminuria, Albuminuria - metabolism, Albuminuria - pathology, Albuminuria - prevention & control, Animals, Antioxidants, Biology and Life Sciences, Blood Glucose - drug effects, Blood Pressure - drug effects, Body weight, Body Weight - drug effects, Care and treatment, Catalase, Catalase - blood, Diabetes, Diabetes mellitus, Diabetes Mellitus, Experimental - drug therapy, Diabetes Mellitus, Experimental - metabolism, Diabetes Mellitus, Experimental - pathology, Diabetic Nephropathies - metabolism, Diabetic Nephropathies - pathology, Diabetic Nephropathies - prevention & control, Diabetic retinopathy, Diabetics, Dipeptidyl-peptidase IV, Dipeptidyl-Peptidase IV Inhibitors - pharmacology, Dipeptidyl-Peptidase IV Inhibitors - therapeutic use, Dosage and administration, Glucose, Glucose 6 phosphate dehydrogenase, Glucosephosphate dehydrogenase, Glucosephosphate Dehydrogenase - genetics, Glucosephosphate Dehydrogenase - metabolism, Health aspects, House mouse, Hypertrophy, Hypoglycemic Agents - pharmacology, Hypoglycemic Agents - therapeutic use, Kidney - drug effects, Kidney - metabolism, Kidney - pathology, Kidneys, Linagliptin, Linagliptin - pharmacology, Linagliptin - therapeutic use, Medical schools, Medicine and Health Sciences, Metabolism, Mice, Mice, Knockout, Oxidative stress, Oxidative Stress - drug effects, Peptidase, Polyclonal antibodies, Proteins, Research and Analysis Methods, Rodents, Streptozocin, Superoxide dismutase, Superoxide Dismutase - blood, Transcription