AIMS/HYPOTHESIS: Diabetic nephropathy is one of the most common forms of chronic kidney disease. The role of adiponectin in the development of diabetic nephropathy has not been elucidated, and the aim of the present study was to investigate the hypothesis that deletion of the gene for adiponectin would accelerate diabetic nephropathy in the Akita mouse. METHODS: We followed four groups of mice from 4 weeks to 16 weeks of age (n ≥ 10 in each group): wild-type (WT) (Ins2 (+/+) Adipoq(+/+)) mice; APN(-/-) (Ins2(+/+) Adipoq(-/-)) mice; Akita (Ins2(+/C96Y) Adipoq(+/+)) mice and Akita/APN(-/-) (Ins2(+/C96Y) Adipoq(-/-)) mice. The mice were then killed and diabetic kidney injury was assessed. In vitro experiments were performed in primary mesangial cells. RESULTS: Mice from both diabetic groups exhibited increased glomerular adiponectin receptor 1 (adipoR1) expression, kidney hypertrophy, glomerular enlargement, increased albuminuria and tissue oxidative stress compared with the WT control. Deletion of the adiponectin gene had no effect on glycaemia. However, Akita/APN(-/-) mice exhibited a greater extent of renal hypertrophy. In vitro, adiponectin attenuated high-glucose-induced phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K). A higher level of fibrosis was observed in the tubulointerstitial and glomerular compartments of the Akita/APN(-/-) mice and adiponectin was found to inhibit TGFβ-induced Smad2 and Smad3 phosphorylation in vitro. There was an exaggerated inflammatory response in the Akita/APN(-/-) mice. Adiponectin also inhibited high-glucose-induced activation of nuclear factor κB (NFκB) in mesangial cells. CONCLUSIONS/ INTERPRETATION: Our data suggest that adiponectin is an important determinant of the kidney response to high glucose in vivo and in vitro.
AIMS/HYPOTHESIS: Diabetic nephropathy is one of the most common forms of chronic kidney disease. The role of adiponectin in the development of diabetic nephropathy has not been elucidated, and the aim of the present study was to investigate the hypothesis that deletion of the gene for adiponectin would accelerate diabetic nephropathy in the Akita mouse. METHODS: We followed four groups of mice from 4 weeks to 16 weeks of age (n ≥ 10 in each group): wild-type (WT) (Ins2 (+/+) Adipoq(+/+)) mice; APN(-/-) (Ins2(+/+) Adipoq(-/-)) mice; Akita (Ins2(+/C96Y) Adipoq(+/+)) mice and Akita/APN(-/-) (Ins2(+/C96Y) Adipoq(-/-)) mice. The mice were then killed and diabetic kidney injury was assessed. In vitro experiments were performed in primary mesangial cells. RESULTS:Mice from both diabetic groups exhibited increased glomerular adiponectin receptor 1 (adipoR1) expression, kidney hypertrophy, glomerular enlargement, increased albuminuria and tissue oxidative stress compared with the WT control. Deletion of the adiponectin gene had no effect on glycaemia. However, Akita/APN(-/-) mice exhibited a greater extent of renal hypertrophy. In vitro, adiponectin attenuated high-glucose-induced phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K). A higher level of fibrosis was observed in the tubulointerstitial and glomerular compartments of the Akita/APN(-/-) mice and adiponectin was found to inhibit TGFβ-induced Smad2 and Smad3 phosphorylation in vitro. There was an exaggerated inflammatory response in the Akita/APN(-/-) mice. Adiponectin also inhibited high-glucose-induced activation of nuclear factor κB (NFκB) in mesangial cells. CONCLUSIONS/ INTERPRETATION: Our data suggest that adiponectin is an important determinant of the kidney response to high glucose in vivo and in vitro.
Authors: T Yamauchi; J Kamon; Y Minokoshi; Y Ito; H Waki; S Uchida; S Yamashita; M Noda; S Kita; K Ueki; K Eto; Y Akanuma; P Froguel; F Foufelle; P Ferre; D Carling; S Kimura; R Nagai; B B Kahn; T Kadowaki Journal: Nat Med Date: 2002-10-07 Impact factor: 53.440
Authors: Sonja Lindfors; Zydrune Polianskyte-Prause; Rim Bouslama; Eero Lehtonen; Miia Mannerla; Harry Nisen; Jukka Tienari; Hanne Salmenkari; Richard Forsgård; Tuomas Mirtti; Markku Lehto; Per-Henrik Groop; Sanna Lehtonen Journal: Diabetologia Date: 2021-05-14 Impact factor: 10.122
Authors: Hoon Suk Park; Ji Hee Lim; Min Young Kim; Yaeni Kim; You Ah Hong; Sun Ryoung Choi; Sungjin Chung; Hyung Wook Kim; Bum Soon Choi; Yong Soo Kim; Yoon Sik Chang; Cheol Whee Park Journal: J Transl Med Date: 2016-06-11 Impact factor: 5.531