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  - JOUR
A1  - von Websky, Karoline
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
T1  - Physiology and pathophysiology of incretins in the kidney
JF  - Current opinion in nephrology and hypertension : reviews of all advances, evaluations of key references, comprehensive listing of papers
N2  - Purpose of reviewIncretin-based therapy with glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is considered a promising therapeutic option for type 2 diabetes mellitus. Cumulative evidence, mainly from preclinical animal studies, reveals that incretin-based therapies also may elicit beneficial effects on kidney function. This review gives an overview of the physiology, pathophysiology, and pharmacology of the renal incretin system.Recent findingsActivation of GLP-1R in the kidney leads to diuretic and natriuretic effects, possibly through direct actions on renal tubular cells and sodium transporters. Moreover, there is evidence that incretin-based therapy reduces albuminuria, glomerulosclerosis, oxidative stress, and fibrosis in the kidney, partially through GLP-1R-independent pathways. Molecular mechanisms by which incretins exert their renal effects are understood incompletely, thus further studies are needed.SummaryThe GLP-1R and DPP-4 are expressed in the kidney in various species. The kidney plays an important role in the excretion of incretin metabolites and most GLP-1R agonists and DPP-4 inhibitors, thus special attention is required when applying incretin-based therapy in renal impairment. Preclinical observations suggest direct renoprotective effects of incretin-based therapies in the setting of hypertension and other disorders of sodium retention, as well as in diabetic and nondiabetic nephropathy. Clinical studies are needed in order to confirm translational relevance from preclinical findings for treatment options of renal diseases.
KW  - DDP-4 inhibition
KW  - diabetes
KW  - diabetic nephropathy
KW  - GLP-1 receptor
KW  - hypertension
KW  - incretins
KW  - kidney
KW  - renal impairment
Y1  - 2014
U6  - https://doi.org/10.1097/01.mnh.0000437542.77175.a0
SN  - 1062-4821
SN  - 1473-6543
VL  - 23
IS  - 1
SP  - 54
EP  - 60
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  -