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: Sachiko Shiba, Kazuhiro Ikeda, Kotaro Azuma, Tomoka Hasegawa, Norio Amizuka, Kuniko Horie-Inoue, Satoshi Inoue
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 453 Issue 3 Pg. 350-5 (Oct 24 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25264202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Carbon-Carbon Ligases
• glutamyl carboxylase
• Glucose

Topics

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