A Variation at Position -30 of the  -Cell Glucokinase Gene Promoter Is Associated With Reduced  -Cell Function in Middle-Aged Japanese-American Men

Diabetes ◽  
1996 ◽  
Vol 45 (4) ◽  
pp. 422-428 ◽  
Author(s):  
L. M. Stone ◽  
S. E. Kahn ◽  
W. Y. Fujimoto ◽  
S. S. Deeb ◽  
D. Porte
Keyword(s):  
Cell Function ◽  
Gene Promoter ◽  
Japanese American ◽  
Middle Aged ◽  
Glucokinase Gene

The g/a Nucleotide Variant at Position -30 in the  -Cell-Specific Glucokinase Gene Promoter Has No Impact on the  -Cell Function in Danish Caucasians

Diabetes ◽  
1998 ◽  
Vol 47 (8) ◽  
pp. 1359-1361 ◽  
Author(s):  
S. A. Urhammer ◽  
T. Hansen ◽  
J. O. Clausen ◽  
H. Eiberg ◽  
O. Pedersen
Keyword(s):  
Cell Function ◽  
Gene Promoter ◽  
Glucokinase Gene

scholarly journals Compromised Function of the Pancreatic Transcription Factor PDX1 in a Lineage of Desert Rodents

2021 ◽  
Author(s):  
Yichen Dai ◽  
Sonia Trigueros ◽  
Peter W. H. Holland
Keyword(s):  
Transcription Factor ◽  
Gene Conversion ◽  
Cell Function ◽  
Protein A ◽  
Gene Promoter ◽  
Homeodomain Protein ◽  
Β Cell ◽  
Desert Rodents ◽  
Biased Gene Conversion ◽  
Β Cell Function

AbstractGerbils are a subfamily of rodents living in arid regions of Asia and Africa. Recent studies have shown that several gerbil species have unusual amino acid changes in the PDX1 protein, a homeodomain transcription factor essential for pancreatic development and β-cell function. These changes were linked to strong GC-bias in the genome that may be caused by GC-biased gene conversion, and it has been hypothesized that this caused accumulation of deleterious changes. Here we use two approaches to examine if the unusual changes are adaptive or deleterious. First, we compare PDX1 protein sequences between 38 rodents to test for association with habitat. We show the PDX1 homeodomain is almost totally conserved in rodents, apart from gerbils, regardless of habitat. Second, we use ectopic gene overexpression and gene editing in cell culture to compare functional properties of PDX1 proteins. We show that the divergent gerbil PDX1 protein inefficiently binds an insulin gene promoter and ineffectively regulates insulin expression in response to high glucose in rat cells. The protein has, however, retained the ability to regulate some other β-cell genes. We suggest that during the evolution of gerbils, the selection-blind process of biased gene conversion pushed fixation of mutations adversely affecting function of a normally conserved homeodomain protein. We argue these changes were not entirely adaptive and may be associated with metabolic disorders in gerbil species on high carbohydrate diets. This unusual pattern of molecular evolution could have had a constraining effect on habitat and diet choice in the gerbil lineage.

scholarly journals Association of postprandial and fasting triglycerides with traits of the metabolic syndrome in the Metabolic Intervention Cohort Kiel

2010 ◽  
Vol 162 (4) ◽  
pp. 719-727 ◽  
Author(s):  
Diana Rubin ◽  
Ulf Helwig ◽  
Michael Nothnagel ◽  
Ulrich R Fölsch ◽  
Stefan Schreiber ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Cell Function ◽  
International Diabetes Federation ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Middle Aged ◽  
The Metabolic Syndrome ◽  
Β Cell Function ◽  
Design And Methods

ObjectivePostprandial (pp) lipid metabolism is associated with insulin resistance and type 2 diabetes. In young men, pp triglycerides (TGs) are more strongly associated with traits of metabolic syndrome (MS) than fasting TGs. We established a cohort of middle-aged men selected for traits of MS and pp lipid metabolism to determine if fasting TGs or pp TGs are more closely related to MS.Research design and methodsA total of 1558 men were characterized for MS. A total of 755 men underwent an oral metabolic tolerance test consisting of a standardized high-fat meal and an oral glucose tolerance test. Blood samples were drawn in the fasting state and hourly until 9 h to determine pp TGs and free fatty acids. Glucose and insulin were analyzed until 5 h pp.ResultsIn the overall cohort, 329 subjects (21.1%) had a complete MS based on the Adult Treatment Panel III criteria, and 650 subjects (41.7%) had a complete MS based on the International Diabetes Federation criteria. The association of pp TGs with MS parameters was not stronger than the association of fasting TGs with them. Pp TGs were independently associated with β-cell function.ConclusionsPp TGs did not show a higher correlation with MS traits than fasting TGs. This finding is probably due to the high incidence of overweight subjects in this middle-aged cohort.

scholarly journals The −30G>A Polymorphism of the Glucokinase Gene Promoter Is Associated With Obesity in a Population From Southern Spain

Obesity ◽  
2008 ◽  
Vol 16 (8) ◽  
pp. 1973-1975 ◽  
Author(s):  
Juan M. Gómez-Zumaquero ◽  
G. Rojo-Martínez ◽  
E. García-Escobar ◽  
Gracia M. Martín-Nuñez ◽  
J. Haro ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Southern Spain ◽  
Glucokinase Gene

Predicting gene promoter methylation in lung tumors through examination of sputum and serum

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7208-7208
Author(s):  
S. A. Belinsky ◽  
M. Grimes ◽  
D. Johnson ◽  
D. Levy ◽  
J. Schiller
Keyword(s):  
Lung Cancer ◽  
Cell Function ◽  
Biological Fluids ◽  
Methylation Status ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Gene Promoter ◽  
Promoter Hypermethylation ◽  
Phase Iii ◽  
Advanced Lung Cancer

7208 Background: Personalized medicine may be a key approach in improving survival for advanced lung cancer. Success for this approach is seen with the response of cancer patients with an activating mutation within the epidermal growth factor receptor to the growth fact inhibitor, gefitinib. Genes involved in all types of normal cell function are targeted for inactivation by promoter hypermethylation during lung cancer development. This makes gene-specific promoter hypermethylation an attractive target for novel treatment strategies. One obstacle to targeted therapy is accessibility of tissue from peripheral tumors for methylation analysis. The purpose of this study was to determine the predictive power of sputum and serum to detect NSCLC through analysis for methylation of genes in these fluids. Methods: Tissue, serum, and sputum were obtained from 72 stage III NSCLC patients participating in a Phase III trial of Carboplatin, Paclitaxel and Radiotherapy, With or Without Thalidomide (ECOG 3598). Methylation specific PCR assessed methylation of the p16, MGMT, DAPK, RASSF1A, PAX5-α, PAX5-β, H-cadherin, and GATA5 genes. Results: At least one gene was methylated in 89% of tumors. Prevalence for methylation ranged from 15–47% and did not differ between gender. Methylation of ≥ 3 genes was seen in ∼50% of tumors. The agreement between sputum or serum in classifying methylation status of any gene in the tumor ranged from 54– 69%. The reduced sensitivity was presumably due in part to absence of tumor DNA in the biological fluids of methylation positive tumors. Logistic regression models revealed 3.1 (CI, 1.2, 8.2) and 4.2 (1.1, 16.1) increased odds for methylation of the p16 and MGMT gene, respectively in tumors if the serum or sputum was positive for methylation. The effect of tumor histology for predicting methylation using sputum and serum is being examined. Conclusion: These studies demonstrate for genes such as p16 and MGMT the possibility of interrogating biological fluids to predict for methylation in the primary tumor. (Supported by CA-89551). No significant financial relationships to disclose.

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