Long-Term Renal Effects of a Neutralizing RAGE Antibody in Obese Type 2 Diabetic Mice

Allan Flyvbjerg, Larry Denner, Bieke F. Schrijvers, Ronald Tilton, Trine H. Mogensen, Søren R. Paludan, Ruth Rasch

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor-mediated pathway and through specific receptors for AGE (RAGEs). To explore a specific role for RAGE in renal changes in type 2 diabetes, we examined the renal effects of a neutralizing murine RAGE antibody in db/db mice, a model of obese type 2 diabetes. One group of db/db mice was treated for 2 months with the RAGE antibody, and another db/db group was treated for the same period with an irrelevant IgG. Two groups of nondiabetic db/+ mice were treated with either RAGE antibody or isotype-matched IgG for 2 months. Placebo-treated db/db mice showed a pronounced increase in kidney weight, glomerular volume, basement membrane thickness (BMT), total mesangial volume, urinary albumin excretion (UAE), and creatinine clearance compared with nondiabetic controls. In RAGE antibody-treated db/db mice, the increase in kidney weight, glomerular volume, mesangial volume, and UAE was reduced, whereas the increase in creatinine clearance and BMT was fully normalized. Notably, these effects in db/db mice were seen without impact on body weight, blood glucose, insulin levels, or food consumption. In conclusion, RAGE is an important pathogenetic factor in the renal changes in an animal model of type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)166-172
Number of pages7
JournalDiabetes
Volume53
Issue number1
DOIs
StatePublished - Jan 2004

Fingerprint

Kidney
Antibodies
Type 2 Diabetes Mellitus
Albumins
Creatinine
Immunoglobulin G
Weights and Measures
Glomerular Basement Membrane
Advanced Glycosylation End Products
Diabetic Nephropathies
Advanced Glycosylation End Product-Specific Receptor
Basement Membrane
Blood Glucose
Animal Models
Placebos
Body Weight
Insulin
Food

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Flyvbjerg, A., Denner, L., Schrijvers, B. F., Tilton, R., Mogensen, T. H., Paludan, S. R., & Rasch, R. (2004). Long-Term Renal Effects of a Neutralizing RAGE Antibody in Obese Type 2 Diabetic Mice. Diabetes, 53(1), 166-172. https://doi.org/10.2337/diabetes.53.1.166

Long-Term Renal Effects of a Neutralizing RAGE Antibody in Obese Type 2 Diabetic Mice. / Flyvbjerg, Allan; Denner, Larry; Schrijvers, Bieke F.; Tilton, Ronald; Mogensen, Trine H.; Paludan, Søren R.; Rasch, Ruth.

In: Diabetes, Vol. 53, No. 1, 01.2004, p. 166-172.

Research output: Contribution to journalArticle

Flyvbjerg, A, Denner, L, Schrijvers, BF, Tilton, R, Mogensen, TH, Paludan, SR & Rasch, R 2004, 'Long-Term Renal Effects of a Neutralizing RAGE Antibody in Obese Type 2 Diabetic Mice', Diabetes, vol. 53, no. 1, pp. 166-172. https://doi.org/10.2337/diabetes.53.1.166
Flyvbjerg A, Denner L, Schrijvers BF, Tilton R, Mogensen TH, Paludan SR et al. Long-Term Renal Effects of a Neutralizing RAGE Antibody in Obese Type 2 Diabetic Mice. Diabetes. 2004 Jan;53(1):166-172. https://doi.org/10.2337/diabetes.53.1.166
Flyvbjerg, Allan ; Denner, Larry ; Schrijvers, Bieke F. ; Tilton, Ronald ; Mogensen, Trine H. ; Paludan, Søren R. ; Rasch, Ruth. / Long-Term Renal Effects of a Neutralizing RAGE Antibody in Obese Type 2 Diabetic Mice. In: Diabetes. 2004 ; Vol. 53, No. 1. pp. 166-172.
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