TY  - JOUR
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Hocher, Berthold
T1  - Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy
JF  - Journal of Molecular Endocrinology
N2  - Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membranebound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure-and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.
KW  - DPP-4
KW  - diabetic nephropathy
KW  - DPP-4 inhibitors
KW  - GLP-1 and SDF-1a
Y1  - 2017
U6  - https://doi.org/10.1530/JME-17-0005
SN  - 0952-5041
SN  - 1479-6813
VL  - 59
SP  - R1
EP  - R10
PB  - Bioscientifica LTD
CY  - Bristol
ER  - 
TY  - GEN
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
T1  - DPP4 inhibition prevents AKI
T2  - Oncotarget
KW  - acute kidney injury
KW  - DPP-4 inhibitors
KW  - ischemia reperfusion injury
KW  - gliptins
KW  - Dipeptidyl peptidase IV
Y1  - 2017
U6  - https://doi.org/10.18632/oncotarget.20212
SN  - 1949-2553
VL  - 8
SP  - 64655
EP  - 64656
PB  - Impact Journals LLC
CY  - Orchard Park
ER  - 
TY  - JOUR
A1  - Sharkovska, Yuliya
A1  - Reichetzeder, Christoph
A1  - Alter, Markus L.
A1  - Tsuprykov, Oleg
A1  - Bachmann, Sebastian
A1  - Secher, Thomas
A1  - Klein, Thomas
A1  - Hocher, Berthold
T1  - Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy
JF  - Journal of hypertension
N2  - Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.
 Method: 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). Results: 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.
 Conclusion: 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.
KW  - diabetic nephropathy
KW  - DPP-4 inhibitors
KW  - linagliptin
Y1  - 2014
U6  - https://doi.org/10.1097/HJH.0000000000000328
SN  - 0263-6352
SN  - 1473-5598
VL  - 32
IS  - 11
SP  - 2211
EP  - 2223
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  -