Hepatic GSK3β-Dependent CRY1 Degradation Contributes to Diabetic Hyperglycemia : Hepatic GSK3 beta -Dependent CRY1 Degradation Contributes to Diabetic Hyperglycemia

Cited 0 time in Web of Science Cited 4 time in Scopus

Kim, Ye Young; Jang, Hagoon; Lee, Gung; Jeon, Yong Geun; Sohn, Jee Hyung; Han, Ji Seul; Lee, Won Taek; Park, Jeu; Huh, Jin Young; Nahmgoong, Hahn; Han, Sang Mun; Kim, Jeesoo; Pak, Minwoo; Kim, Sun; Kim, Jong-Seo; Kim, Jae Bum

Issue Date
American Diabetes Association
Diabetes, Vol.71 No.7, pp.1373-1387
© 2022 by the American Diabetes Association.Excessive hepatic glucose production (HGP) is a key factor promoting hyperglycemia in diabetes. Hepatic cryptochrome 1 (CRY1) plays an important role in maintaining glucose homeostasis by suppressing forkhead box O1 (FOXO1)-mediated HGP. Although downregulation of hepatic CRY1 appears to be associated with increased HGP, the mechanism(s) by which hepatic CRY1 dysregulation confers hyperglycemia in subjects with diabetes is largely unknown. In this study, we demonstrate that a reduction in hepatic CRY1 protein is stimulated by elevated E3 ligase F-box and leucine-rich repeat protein 3 (FBXL3)-dependent proteasomal degradation in diabetic mice. In addition, we found that GSK3β-induced CRY1 phosphorylation potentiates FBXL3-dependent CRY1 degradation in the liver. Accordingly, in diabetic mice, GSK3β inhibitors effectively decreased HGP by facilitating the effect of CRY1-mediated FOXO1 degradation on glucose metabolism. Collectively, these data suggest that tight regulation of hepatic CRY1 protein stability is crucial for maintaining systemic glucose homeostasis.
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Computer Science and Engineering (컴퓨터공학부)Journal Papers (저널논문_컴퓨터공학부)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.