Endocrinology and Metabolism

Brief Report

Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing: Eun-Hee Cho, Jae Woong Min, Sun Shim Choi, Hoon Sung Choi, Sang-Wook Kim; Endocrinol Metab. 2017;32(2):296-301. Published online May 29, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.296; Correction in: Endocrinol Metab 2021;36(2):468

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Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.

Citations

Citations to this article as recorded by

Two novel GCK mutations in Chinese patients with maturity-onset diabetes of the young
Tao Wang, Mengmeng Zhu, Yun Wang, Cheng Hu, Chen Fang, Ji Hu
Endocrine.2023; 83(1): 92. CrossRef
Maturity-onset diabetes of the young in a large Portuguese cohort
Sílvia Santos Monteiro, Tiago da Silva Santos, Liliana Fonseca, Guilherme Assunção, Ana M. Lopes, Diana B. Duarte, Ana Rita Soares, Francisco Laranjeira, Isaura Ribeiro, Eugénia Pinto, Sónia Rocha, Sofia Barbosa Gouveia, María Eugenia Vazquez-Mosquera, Ma
Acta Diabetologica.2022; 60(1): 83. CrossRef
Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options
Hazar Younis, Se Eun Ha, Brian G. Jorgensen, Arushi Verma, Seungil Ro
Journal of Personalized Medicine.2022; 12(11): 1762. CrossRef
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Kyung Mi Jang
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Diabetes Research and Clinical Practice.2021; 171: 108553. CrossRef
Etiologic distribution and clinical characteristics of pediatric diabetes in 276 children and adolescents with diabetes at a single academic center
Ja Hye Kim, Yena Lee, Yunha Choi, Gu-Hwan Kim, Han-Wook Yoo, Jin-Ho Choi
BMC Pediatrics.2021;[Epub] CrossRef
Gençlerin Erişkin Başlangıçlı Diyabeti (MODY) Sorumlu HNF4A, GCK ve HNF1 Gen Varyasyonlarının Dünya Genelinde Coğrafik Dağılımı
Deniz KANCA DEMİRCİ, Nurdan GÜL, İlhan SATMAN, Oguz OZTURK, Hülya YILMAZ AYDOĞAN
Haliç Üniversitesi Fen Bilimleri Dergisi.2021; 4(1): 41. CrossRef
Undernutrition and suboptimal growth during the first year are associated with glycemia but not with insulin resistance in adulthood
Isabel Pereyra, Sandra López-Arana, Bernardo L. Horta
Cadernos de Saúde Pública.2021;[Epub] CrossRef
Update on Monogenic Diabetes in Korea
Ye Seul Yang, Soo Heon Kwak, Kyong Soo Park
Diabetes & Metabolism Journal.2020; 44(5): 627. CrossRef
The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)
Ken Munene Nkonge, Dennis Karani Nkonge, Teresa Njeri Nkonge
Clinical Diabetes and Endocrinology.2020;[Epub] CrossRef
Novel deletion mutation in the glucokinase gene from a Korean man with GCK-MODY phenotype and situs inversus
Yun Kyung Cho, Eun-Hee Cho, Hoon Sung Choi, Sang-Wook Kim
Diabetes Research and Clinical Practice.2018; 143: 263. CrossRef

Original Article

Glucose Regulated Production of Human Insulin in Genetically Modified Myoblast Cell Line (C2C12).: Seungjoon Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2006;21(6):526-535. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.526

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Abstract PDF: BACKGROUND
To develop somatic gene therapy model for diabetes mellitus, it is the most important to control it by glucose concentration. In order to develop the myoblasts that produce insulin by glucose concentration, the transfection of genes of human insulin, rat glucokinase and rat GLUT2 was conducted using C2C12, the murine myoblast cell line. METHODS: pMLC-hINSmut plasmid vector to which human insulin cDNA was inserted in C2C12 cell line, pCB7/GLUT2 and pCB7/GK to which GLUT2 and glucokinase were inserted. Based on the inserted gene, C2C12/INS-GLUT2, C2C12/INS-GK and C2C12/INS-GK-GLUT2 were prepared. In each cell line, its mRNA and protein expression were measured. Also, the capability of producing insulin in low glucose (2.7 mM) and high glucose (25 mM) were compared. RESULTS: 1. It was observed that C2C12/INS-GLUT2, C2C12/INS-GK, C2C12/INS-GK-GLUT2 cell line expressed mRNA and protein of transfected genes, respectively. 2. As for the insulin production depending on the glucose concentration in C2C12/INS, it slightly increased from 0.049 +/- 0.003 micro U/10(6) cells/hr to 0.197 +/- 0.022 micro U/10(6) cells/hr. However, in C2C12/GK-GLUT2-INS, it showed the most evident increase: from 0.251 +/- 0.074 micro U/10(6) cells/hr to 1.325 +/- 0.221 micro U/10(6) cells/hr. 3. The expression of insulin gene decreased in proportion to the insulin production capability, reaching the minimum point at the 8th week. CONCLUSION: Genetically engineered murine myoblast secreted insulin depending on the glucose concentration in vitro and was able to cause its decrement when transplanted. However, it should be continued to study the method to maintain the consistent genetic expression in somatic cell therapy.

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