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
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
Externí odkaz: