Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy
- 1 November 2014
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Hypertension
- Vol. 32 (11), 2211-2223
- https://doi.org/10.1097/hjh.0000000000000328
Abstract
Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear. This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes. Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril. Ten-week-old male diabetic db/db mice were treated for 3 months with either vehicle (n = 10), 3 mg linagliptin/kg per day (n = 8), or 20 mg enalapril/kg per day (n = 10). Heterozygous db/m mice treated with vehicle served as healthy controls (n = 8). Neither linagliptin nor enalapril had significant effects on the parameters of glucose metabolism or blood pressure in diabetic db/db mice. However, linagliptin treatment reduced albuminuria and attenuated kidney injury. In addition, expression of podocyte marker podocalyxin was normalized. We also analysed DPP-4 expression by immunofluorescence in human kidney biopsies and detected upregulation of DPP-4 in the glomeruli of patients with diabetic nephropathy, suggesting that our findings might be of relevance for human kidney disease as well. Treatment with DPP-4 inhibitor linagliptin delays the progression of diabetic nephropathy damage in a glucose-independent and blood-pressure-independent manner. The observed effects may be because of the attenuation of podocyte injury and inhibition of myofibroblast transformation.This publication has 51 references indexed in Scilit:
- Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic miceAmerican Journal of Physiology-Renal Physiology, 2012
- Renal and Cardiac Effects of DPP-4 Inhibitors – from Preclinical Development to Clinical ResearchKidney and Blood Pressure Research, 2012
- Dipeptidyl Peptidase IV Inhibitor Attenuates Kidney Injury in Streptozotocin-Induced Diabetic RatsThe Journal of pharmacology and experimental therapeutics, 2011
- High mobility group box 1 is a novel substrate of dipeptidyl peptidase-IVDiabetologia, 2011
- Peptidase substrates via global peptide profilingNature Chemical Biology, 2008
- Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 DiabetesThe New England Journal of Medicine, 2008
- Effects of Intensive Glucose Lowering in Type 2 DiabetesThe New England Journal of Medicine, 2008
- Diabetic Nephropathy: Mechanisms of Renal Disease ProgressionExperimental Biology and Medicine, 2008
- The biology of incretin hormonesCell Metabolism, 2006
- Dipeptidyl‐peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon‐like peptide‐1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serumJBIC Journal of Biological Inorganic Chemistry, 1993