title: γ-Glutamyl carboxylase in osteoblasts regulates glucose metabolism in mice.
abstract: Vitamin K-dependent γ-glutamyl carboxylase (GGCX) is an enzyme that catalyzes the conversion of glutamic acid to gamma-carboxyglutamic acid in substrate proteins. Among GGCX target proteins, recent evidence indicates that osteocalcin regulates insulin sensitivity and secretion. However, the precise contribution of GGCX to glucose metabolism remains to be clarified. To address this question, we generated osteoblast-specific Ggcx-deficient (i.e., conditional knockout [cKO]) mice using collagen type 1 α1 (Col1)-Cre mice. Ggcx cKO mice exhibited altered metabolism compared with their controls; serum glucose levels could be maintained with low amounts of insulin, and the weight of white adipose tissue (WAT) significantly decreased in Ggcx cKO mice. Our findings suggest that GGCX expressed in osteoblasts is critical for the maintenance of blood glucose and WAT.
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Shiba
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Developmental Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Developmental Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie-Inoue
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: INOUE-GER@h.u-tokyo.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000818:Animals; D019735:Carbon-Carbon Ligases / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000201:enzymology*
chemical_list: D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D005947:Glucose
keywords: Conditional knockout mice; GGCX; Glucose metabolism; Osteocalcin; Vitamin K