In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy

Masaomi Nangaku, Yuko Izuhara, Nobuteru Usuda, Reiko Inagi, Takeo Shibata, Satoshi Sugiyama, Kiyoshi Kurokawa, Charles van Ypersele de Strihou, Toshio Miyata

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Background. The present study has been undertaken to unravel the critical factors involved in the progression of diabetic nephropathy (DN). Methods. A unique type 2 diabetic rat model with a wide range of metabolic derangements and hypertension has been utilized, the spontaneously hypertensive-NIH-corpulent rat SHR-NDmcr-cp(cp/cp). It develops histologically evident glomerular injury and tubulointerstitial damage, including mesangial activation, podocyte injury, and inflammatory cell infiltration in the tubulointerstitium. Results. A low calorie diet for 22 weeks significantly improves obesity, proteinuria and renal morphological alterations. The correction of renal injury is independent of blood pressure control. Obesity correction, although partial, normalizes the renal content of pentosidine taken as a marker of oxidative stress and advanced glycation end products (AGEs). This occurs despite the fact that, in this model, improvement of glucose control and hyperlipidaemia is limited. Proteinuria and body weight are highly correlated with renal pentosidine content, while proteinuria and body weight are also correlated with each other. Diabetic renal injury is thus inhibited by a low calorie diet with an attendant reduction of oxidative stress and AGE formation, despite sustained hypertension. Conclusion. The present findings suggest a direct role of obesity in the generation of a localized oxidative stress and AGE formation, directly responsible for DN.

Original languageEnglish
Pages (from-to)2661-2669
Number of pages9
JournalNephrology Dialysis Transplantation
Volume20
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Keywords

  • Advanced glycation end product
  • Multiple risk factor intervention
  • Pentosidine
  • Proteinuria
  • Renoprotection

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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