title: Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy.
abstract: BACKGROUND
  Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aInstitute of Vegetative Anatomy, Charite Universitätsmedizin Berlin bCenter for Cardiovascular Research, Institute of Pharmacology, Charité cUniversity of Potsdam, Potsdam dDepartment of Nephrology, Charité Campus Benjamin Franklin, Berlin, Germany eGubra, Copenhagen, Denmark fBoehringer Ingelheim, Biberach, Germany.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Sharkovska
authors.forename: Christoph
authors.initials: C
authors.lastname: Reichetzeder
authors.forename: Markus
authors.initials: M
authors.lastname: Alter
authors.forename: Oleg
authors.initials: O
authors.lastname: Tsuprykov
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Secher
authors.forename: Thomas
authors.initials: T
authors.lastname: Klein
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004656:Enalapril / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D000069476:Linagliptin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D004656:Enalapril; D005947:Glucose