title: The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.
abstract: Diabetic nephropathy is the leading cause of end-stage renal disease in humans in the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose excretion. Whether this strategy exerts beneficial effects on the development of type 2 diabetic nephropathy is still largely unclear. We investigated the effects of the specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep<ob>/WiscJ (BTBR ob/ob) mice, which spontaneously develop type 2 diabetic nephropathy. In the first experiment, BTBR ob/ob mice received either a diet containing 300 ppm empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, BTBR ob/ob mice received 1 μg·kg body wt(-1)·day(-1) ANG II to induce arterial hypertension and were separated into the same two diet groups for 6 wk. In both experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood glucose. Independently of hypertension, empagliflozin reduced albuminuria in diabetic mice. However, empagliflozin treatment affected diabetes-related glomerular hypertrophy, markers of renal inflammation, and mesangial matrix expansion only in BTBR ob/ob mice without hypertension. In summary, empagliflozin demonstrated significant antihyperglycemic effects, differentially ameliorating early features of diabetic nephropathy in BTBR ob/ob mice with and without hypertension.
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Florian
authors.initials: F
authors.lastname: Gembardt
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bartaun
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Natalia
authors.initials: N
authors.lastname: Jarzebska
authors.affiliation: Divison of Research, Boehringer Ingelheim Pharma, Biberach/Riss, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Mayoux
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Vladimir T
authors.initials: VT
authors.lastname: Todorov
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hohenstein
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and christian.hugo@uniklinikum-dresden.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Hugo
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications* / Q000453:epidemiology; D006984:Hypertrophy / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000453:epidemiology; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C490299:Slc5a2 protein, mouse; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: BTBR.Cg-Lep<ob>/WiscJ; Na+-glucose cotransporters; diabetes mellitus type 2; diabetic nephropathy; hypertension; renal growth