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Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient

Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in... Transglutaminase 2 (TGase 2) is a Ca+2‐ dependent enzyme that catalyzes both intracellular and extracellular cross‐linking reactions by transamidation of specific glutamine residues. TGase 2 is known to be involved in the membrane‐mediated events required for glucose‐stimulated insulin release from the pancreatic β cells. Here we show that targeted disruption of TGase 2 impairs glucose‐stimulated insulin secretion. TGase 2‐/‐mice show glucose intolerance after intraperitoneal glucose loading. TGase 2‐/‐mice manifest a tendency to develop hypoglycemia after administration of exogenous insulin as a consequence of enhanced insulin receptor substrate 2 (IRS‐2) phosphorylation. We suggest that the increased peripheral sensitivity to insulin partially compensates for the defective secretion in this animal model. TGase 2‐/‐mouse phenotype resembles that of the maturity‐onset diabetes of young (MODY) patients. In the course of screening for human TGase 2 gene in Italian subjects with the clinical features of MODY, we detected a missense mutation (N333S) in the active site of the enzyme. Collectively, these results identify TGase 2 as a potential candidate gene in type 2 diabetes.—Bernassola, F., Federici, M., Corazzari, M., Terrinoni, A., Hribal, M. L., De Laurenzi, V., Ranalli, M., Massa, O., Sesti, G., Mclean, W. H. I., Citro, G., Barbetti, F., Melino, G. Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient. FASEB J. 16, 1371–1378 (2002) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The FASEB Journal Wiley

Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient

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References (49)

Publisher
Wiley
Copyright
© Federation of American Societies for Experimental Biology
eISSN
1530-6860
DOI
10.1096/fj.01-0689com
Publisher site
See Article on Publisher Site

Abstract

Transglutaminase 2 (TGase 2) is a Ca+2‐ dependent enzyme that catalyzes both intracellular and extracellular cross‐linking reactions by transamidation of specific glutamine residues. TGase 2 is known to be involved in the membrane‐mediated events required for glucose‐stimulated insulin release from the pancreatic β cells. Here we show that targeted disruption of TGase 2 impairs glucose‐stimulated insulin secretion. TGase 2‐/‐mice show glucose intolerance after intraperitoneal glucose loading. TGase 2‐/‐mice manifest a tendency to develop hypoglycemia after administration of exogenous insulin as a consequence of enhanced insulin receptor substrate 2 (IRS‐2) phosphorylation. We suggest that the increased peripheral sensitivity to insulin partially compensates for the defective secretion in this animal model. TGase 2‐/‐mouse phenotype resembles that of the maturity‐onset diabetes of young (MODY) patients. In the course of screening for human TGase 2 gene in Italian subjects with the clinical features of MODY, we detected a missense mutation (N333S) in the active site of the enzyme. Collectively, these results identify TGase 2 as a potential candidate gene in type 2 diabetes.—Bernassola, F., Federici, M., Corazzari, M., Terrinoni, A., Hribal, M. L., De Laurenzi, V., Ranalli, M., Massa, O., Sesti, G., Mclean, W. H. I., Citro, G., Barbetti, F., Melino, G. Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient. FASEB J. 16, 1371–1378 (2002)

Journal

The FASEB Journal – Wiley

Published: Sep 1, 2002

Keywords: insulin; diabetes; mature‐onset diabetes of the young

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