γ-Glutamyl carboxylase in osteoblasts regulates glucose metabolism in mice

Biochem Biophys Res Commun. 2014 Oct 24;453(3):350-5. doi: 10.1016/j.bbrc.2014.09.091. Epub 2014 Sep 27.

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.

Keywords: Conditional knockout mice; GGCX; Glucose metabolism; Osteocalcin; Vitamin K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon-Carbon Ligases / genetics
  • Carbon-Carbon Ligases / metabolism*
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Male
  • Mice
  • Mice, Knockout
  • Osteoblasts / enzymology*

Substances

  • Carbon-Carbon Ligases
  • glutamyl carboxylase
  • Glucose