Glucokinase Gene May Be a More Suitable Target Than the Insulin Gene for Detection of β Cell Death

Endocrinology
Jana SklenarovaOndrej Cinek

Abstract

Detection and quantification of unmethylated circulating insulin (INS) DNA presumably released from β cells has been previously used for assessing their destruction. As the targets within the INS gene suffer from suboptimal specificity, we sought to improve the assay parameters by using the glucokinase gene (GCK) tissue-specific pancreatic promoter. The amount of methylated and unmethylated GCK DNA was measured using a droplet polymerase chain reaction assay and compared with the previously published INS-targeted assay. The method was tested using synthetic target sequences and DNA from pancreatic islets, blood, brain, kidney, large intestine, liver, lung, small intestine, and stomach. Circulating serum DNA was obtained from children with recent-onset type 1 diabetes (T1D) (n = 25), autoantibody-positive first-degree relatives of T1D patients (n = 14), and healthy controls (n = 20). The unmethylated GCK DNA was found to be more islet specific than unmethylated INS DNA. The proportion of the unmethylated GCK DNA was lower than INS in all tested extrapancreatic tissues, except kidney. Although the amounts of methylated DNA measured by the two assays were similar, the INS assay detected considerably more unmethylated DNA. Whereas ...Continue Reading

References

Aug 30, 2008·Cellular and Molecular Life Sciences : CMLS·P B Iynedjian
Oct 8, 2008·Annals of the New York Academy of Sciences·Ruth E BoardAndrew Hughes
Mar 14, 2009·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiaoyan XuePenella J Woll
Nov 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Eitan M AkiravKevan C Herold
Jun 4, 2013·Clinica Chimica Acta; International Journal of Clinical Chemistry·Safia El MessaoudiAlain R Thierry
Jul 9, 2014·Endocrinology·Sahar Usmani-BrownMichel Ledizet
Feb 3, 2015·The Journal of Clinical Investigation·Kevan C HeroldUNKNOWN Type 1 Diabetes TrialNet Study Group
Dec 8, 2015·Diabetic Medicine : a Journal of the British Diabetic Association·L PetruzelkovaS Kolouskova

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Citations

Jun 25, 2019·Expert Review of Proteomics·Ernesto S NakayasuThomas O Metz
Sep 1, 2018·Current Diabetes Reports·Laura M JacobsenTodd M Brusko
Aug 17, 2018·Diabetologia·Emily K SimsRaghavendra G Mirmira
Mar 7, 2021·International Journal of Molecular Sciences·Marilyn ArosemenaRaghavendra G Mirmira

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