scholarly journals CHRM3 Gene Variation Is Associated With Decreased Acute Insulin Secretion and Increased Risk for Early-Onset Type 2 Diabetes in Pima Indians

Diabetes ◽  
2006 ◽  
Vol 55 (12) ◽  
pp. 3625-3629 ◽  
Author(s):  
Y. Guo ◽  
M. Traurig ◽  
L. Ma ◽  
S. Kobes ◽  
I. Harper ◽  
...  
Diabetes ◽  
2008 ◽  
Vol 57 (11) ◽  
pp. 3156-3160 ◽  
Author(s):  
L. Ma ◽  
R. L. Hanson ◽  
L. N. Que ◽  
Y. Guo ◽  
S. Kobes ◽  
...  

2012 ◽  
Vol 48 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Neil W Salter ◽  
Sudharsana R Ande ◽  
Hoa K Nguyen ◽  
B L Grégoire Nyomba ◽  
Suresh Mishra

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.


Thyroid ◽  
2012 ◽  
Vol 22 (1) ◽  
pp. 80-87 ◽  
Author(s):  
Saraswathy Nair ◽  
Yunhua Li Muller ◽  
Emilio Ortega ◽  
Sayuko Kobes ◽  
Clifton Bogardus ◽  
...  

2021 ◽  
pp. 1-11
Author(s):  
Baizid Khoorshid Riaz ◽  
Shahjada Selim ◽  
Megan Neo ◽  
Md Nazmul Karim ◽  
M. Mostafa Zaman

<b><i>Methodology:</i></b> Biochemically confirmed type 2 diabetes mellitus (T2DM) patients (<i>n</i> = 1,114) were recruited from the outpatient department of 2 tertiary care hospitals in Dhaka, Bangladesh. Face-to-face interview was conducted using a semi-structured questionnaire containing sociodemographic parameters and relevant information about depression and diabetes. Biochemical test results and treatment-related information were taken from patients’ records. The Hospital Anxiety and Depression Scale (HADS) was used to screen all patients for psychiatric manifestation. Those diagnosed by HADS were subsequently reassessed using structured clinical interview for DSM-5 Disorders – Clinician Version. T2DM diagnosed at age &#x3c;40 years were considered as early onset T2DM. Association between age of onset category and depression was assessed using multivariable mixed-effect logistic regression adjusting for random variation of the area of residence and plausible confounders. <b><i>Results:</i></b> Around a third of the participants (32.5%) were diagnosed with T2DM before the age of 40 years. Early onset T2DM patients were found to have 57% increase in the risk of developing depression (OR 1.57; 95% CI 1.13–2.28; <i>p</i> = 0.011) in comparison to those with usual onset T2DM (≥40 years). Among other factors a positive family history for diabetes (OR 1.33; 95% CI 1.03–1.78; <i>p</i> = 0.038), poor glycemic control (OR 1.31; 95% CI 1.03–1.68; <i>p</i> = 0.028), presence of 1, or more diabetic complications (OR 1.37; 95% CI 1.03–1.78; <i>p</i> = 0.011) also showed increased risk of depression. <b><i>Conclusion:</i></b> Early onset T2DM patients are at greater risk of developing depression. The finding is likely to help in setting preventive strategies aiming to reduce the presence of concomitant depression symptoms among diabetes.


Diabetologia ◽  
2021 ◽  
Author(s):  
Amélie Keller ◽  
Fanney Thorsteinsdottir ◽  
Maria Stougaard ◽  
Isabel Cardoso ◽  
Peder Frederiksen ◽  
...  

2007 ◽  
Vol 28 (11) ◽  
pp. 1150-1150 ◽  
Author(s):  
O. Porzio ◽  
O. Massa ◽  
V. Cunsolo ◽  
C. Colombo ◽  
M. Malaponti ◽  
...  

2013 ◽  
Vol 72 (1) ◽  
pp. 21190 ◽  
Author(s):  
Julia D. Rempel ◽  
Juliet Packiasamy ◽  
Heather J. Dean ◽  
Jonathon McGavock ◽  
Alyssa Janke ◽  
...  

2017 ◽  
Vol 15 (9) ◽  
pp. 458-464 ◽  
Author(s):  
Gadadharan Vijayakumar ◽  
Ganapathy K. Sreehari ◽  
Aswathi Vijayakumar ◽  
Abdul Jaleel

Sign in / Sign up

Export Citation Format

Share Document