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

Authors: Bernassola, F  Federici, M  Corazzari, M  Terrinoni, A  Hribal, ML  De Laurenzi, V  Ranalli, M  Massa, O  Sesti, G  McLean, WH  Citro, G  Barbetti, F  Melino, G 
Citation: Bernassola F, etal., FASEB J. 2002 Sep;16(11):1371-8.
Pubmed: (View Article at PubMed) PMID:12205028
DOI: Full-text: DOI:10.1096/fj.01-0689com

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 beta 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.


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CRRD Object Information
CRRD ID: 1579997
Created: 2006-06-14
Species: All species
Last Modified: 2006-06-14
Status: ACTIVE


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