scholarly journals Missense mutations in theTGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes

2007 ◽  
Vol 28 (11) ◽  
pp. 1150-1150 ◽  
Author(s):  
O. Porzio ◽  
O. Massa ◽  
V. Cunsolo ◽  
C. Colombo ◽  
M. Malaponti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Early Onset ◽  
Transglutaminase 2 ◽  
Missense Mutations ◽  
Gene Encoding ◽  
Onset Type

scholarly journals Functional characterization of naturally occurring transglutaminase 2 mutants implicated in early-onset type 2 diabetes

2012 ◽  
Vol 48 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Neil W Salter ◽  
Sudharsana R Ande ◽  
Hoa K Nguyen ◽  
B L Grégoire Nyomba ◽  
Suresh Mishra
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Early Onset ◽  
Intracellular Signaling ◽  
Transglutaminase 2 ◽  
Second Phase ◽  
Onset Type ◽  
Gtp Binding ◽  
Naturally Occurring

Transglutaminase 2 (TG2) is an enzyme with diverse biological functions. TG2 catalyzes transamidation reactions, has intrinsic kinase activity, and acts as a G-protein in intracellular signaling. TG2 (Tgm2)-null mice are glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS). Furthermore, three naturally occurring missense mutations in the human TGM2 gene, corresponding to amino acid substitutions of Met330Arg, Ile331Asn, and Asn333Ser in the TG2 protein, have been reported and found to be associated with early-onset type 2 diabetes. However, their effect on TG2 function is not fully understood. To determine this, we have reproduced naturally occurring mutations in TG2 using site-directed mutagenesis. Overexpression of Myc-TG2 mutants in INS-1E cells resulted in a reduction of GSIS in comparison with cells overexpressing wild-type Myc-TG2 (WT-TG2). The maximum reduction was found in cells overexpressing Ile331Asn-TG2 (32%) followed by Met330Arg-TG2 (20%), and the least in Asn333Ser-TG2 (7%). Enzymatic analysis revealed that TG2 mutants have impaired transamidation and kinase activities in comparison with WT-TG2. GTP-binding assays showed that TG2 mutants also have altered GTP-binding ability, which is found to be modulated in response to glucose stimulation. Collectively, these data suggest that naturally occurring mutations in TG2 affect transamidation, kinase, and GTP-binding functions of TG2. While reduced insulin secretion, as a result of naturally occurring mutations in TG2, is due to the impairment of more than one biological function of TG2, it is the transamidation function that appears to be impaired during the first phase, whereas the GTP-binding function affects the second phase of insulin secretion.

Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study

Diabetologia ◽  
2021 ◽  
Author(s):  
Amélie Keller ◽  
Fanney Thorsteinsdottir ◽  
Maria Stougaard ◽  
Isabel Cardoso ◽  
Peder Frederiksen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin D ◽  
Cohort Study ◽  
Early Onset ◽  
Dried Blood Spots ◽  
Onset Type ◽  
Blood Spots

scholarly journals Preliminary analysis of immune activation in early onset type 2 diabetes

2013 ◽  
Vol 72 (1) ◽  
pp. 21190 ◽  
Author(s):  
Julia D. Rempel ◽  
Juliet Packiasamy ◽  
Heather J. Dean ◽  
Jonathon McGavock ◽  
Alyssa Janke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Activation ◽  
Early Onset ◽  
Preliminary Analysis ◽  
Onset Type

Distinct Predictors and Comorbidities in Early Onset Type 2 Diabetes Mellitus Among Asian Indians

2017 ◽  
Vol 15 (9) ◽  
pp. 458-464 ◽  
Author(s):  
Gadadharan Vijayakumar ◽  
Ganapathy K. Sreehari ◽  
Aswathi Vijayakumar ◽  
Abdul Jaleel
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Early Onset ◽  
Asian Indians ◽  
Onset Type
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