title: Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice.
abstract: We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman's capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes.
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Albrecht
authors.affiliation: The Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Schilperoort
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Jana D
authors.initials: JD
authors.lastname: Braun
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Jiedong
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Angelica
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Diego O
authors.initials: DO
authors.lastname: Pastene
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Köppel
authors.affiliation: The Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Baelde
authors.affiliation: The Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.affiliation: The Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Anna Altomare
authors.affiliation: The Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Regazzoni
authors.affiliation: The Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Denisi
authors.affiliation: The Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Aldini
authors.affiliation: Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
authors.affiliation: Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Sibylle J
authors.initials: SJ
authors.lastname: Hauske
mesh_terms: D000284:Administration, Oral; D000419:Albuminuria / Q000097:blood / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002336:Carnosine / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009929:Organ Size / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D002336:Carnosine; D004150:Dipeptidases; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C019673:aminoacyl-histidine dipeptidase