title: Ablation of Rnf213 retards progression of diabetes in the Akita mouse.
abstract: Moyamoya disease (MMD) and moyamoya syndrome are vasculopathies characterized by progressive stenosis in the circle of Willis and its branches. The RNF213 gene, which encodes a novel class of proteins, characterized by both E3 ligase and AAA+ATPase activities, has been identified as the susceptibility gene for MMD. However, its physiological functions remain unknown. MMD and moyamoya syndrome are often accompanied by diabetes mellitus. In this study, we generated Rnf213 knockout (KO) C57BL/6 mice (Rnf213(-/-); Ins2(+/+)), which were mated with Akita (C57BL/6 Rnf213(+/+); Ins2(+/C96Y)) mice, a strain that develops diabetes spontaneously by 5 weeks of age, to obtain mice lacking Rnf213 and carrying the Akita mutation (KO/Akita, Rnf213(-/-); Ins2(+/C96Y)). Body weight and blood glucose concentration were measured from 6 to 20 weeks. Glucose tolerance, insulin resistance, plasma insulin and leptin concentrations, food consumption, pancreatic insulin content and histopathology were evaluated at 18 weeks of age. We found that glucose tolerance, as indicated by AUC, was 20% lower (p<0.05) and insulin contents in pancreas were 150% higher (p<0.05), in KO/Akita than in Akita mice. The number of CHOP positive β-cells assayed by histopathological examination was 30% lower and food consumption was 34% lower in KO/Akita than in Akita mice (p<0.05 each). These findings indicated that the disruption of Rnf213 improved glucose tolerance by protecting islet β cells.
authors: Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Hatasu
authors: H
authors: Kobayashi
authors: Satoru
authors: S
authors: Yamazaki
authors: Seiji
authors: S
authors: Takashima
authors: Wanyang
authors: W
authors: Liu
authors: Hiroko
authors: H
authors: Okuda
authors: Junxia
authors: J
authors: Yan
authors: Yukiko
authors: Y
authors: Fujii
authors: Toshiaki
authors: T
authors: Hitomi
authors: Kouji H
authors: KH
authors: Harada
authors: Toshiyuki
authors: T
authors: Habu
authors: Akio
authors: A
authors: Koizumi
mesh_terms: D000251:Adenosine Triphosphatases; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000209:etiology / Q000473:pathology*; D018450:Disease Progression; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000648:ultrastructure; D020738:Leptin / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009072:Moyamoya Disease / Q000150:complications* / Q000235:genetics; D051742:Transcription Factor CHOP / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C497250:Ddit3 protein, mouse; D007328:Insulin; D020738:Leptin; D051742:Transcription Factor CHOP; C583291:RNF213 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases