| First Author | Fang F | Year | 2015 |
| Journal | Diabetologia | Volume | 58 |
| Issue | 7 | Pages | 1668-78 |
| PubMed ID | 25957229 | Mgi Jnum | J:224619 |
| Mgi Id | MGI:5688430 | Doi | 10.1007/s00125-015-3605-9 |
| Citation | Fang F, et al. (2015) Deletion of the gene for adiponectin accelerates diabetic nephropathy in the Ins2 (+/C96Y) mouse. Diabetologia 58(7):1668-78 |
| abstractText | 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 TGFbeta-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 kappaB (NFkappaB) 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. |
