scholarly journals Cell-biological assessment of human glucokinase mutants causing maturity-onset diabetes of the young type 2 (MODY-2) or glucokinase-linked hyperinsulinaemia (GK-HI)

1999 ◽  
Vol 342 (2) ◽  
pp. 345-352 ◽  
Author(s):  
Charlotte V. BURKE ◽  
Carol W. BUETTGER ◽  
Elizabeth A. DAVIS ◽  
Steven J. MCCLANE ◽  
Franz M. MATSCHINSKY ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Human Islet ◽  
Biological Assessment ◽  
Hill Coefficient ◽  
Published Data ◽  
Mrna Levels ◽  
Maturity Onset Diabetes ◽  
Wild Type ◽  
Onset Diabetes

Mutations in the glucokinase (GK) gene cause type-2 maturity-onset diabetes of the young type 2 (MODY-2) and GK-linked hyperinsulinaemia (GK-HI). Recombinant adenoviruses expressing the human wild-type islet GK or one of four mutant forms of GK, (the MODY-2 mutants E70K, E300K and V203A and the GK-HI mutant V455M) were transduced into glucose-responsive insulin-secreting β-HC9 cells and tested functionally in order to initiate the first analysis in vivoof recombinant wild-type and mutant human islet GK. Kinetic analysis of wild-type human GK showed that the glucose S0.5 and Hill coefficient were similar to previously published data in vitro (S0.5 is the glucose level at the half-maximal rate). E70K had half the glucose affinity of wild-type, but similar enzyme activity. V203A demonstrated decreased catalytic activity and an 8-fold increase in glucose S0.5 when compared with wild-type human islet GK. E300K had a glucose S0.5 similar to wild-type but a 10-fold reduction in enzyme activity. E300K mRNA levels were comparable with wild-type GK mRNA levels, but Western-blot analyses demonstrated markedly reduced levels of immunologically detectable protein, consistent with an instability mutation. V455M was just as active as wild-type GK, but with a markedly reduced S0.5. The effects of the different GK mutants on glucose-stimulated insulin release support the kinetic and expression data. These experiments show the utility of a combined genetic, biochemical and cell-biological approach to the quantification of functional and structural changes of human GK that result from MODY-2 and GK-HI mutations.

scholarly journals Structural instability of mutant β-cell glucokinase: implications for the molecular pathogenesis of maturity-onset diabetes of the young (type-2)

1997 ◽  
Vol 322 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Prabakaran KESAVAN ◽  
Liqun WANG ◽  
Elizabeth DAVIS ◽  
Antonio CUESTA ◽  
Ian SWEET ◽  
...  
Keyword(s):  
Structural Instability ◽  
Pancreatic Β Cell ◽  
Maturity Onset Diabetes ◽  
Wild Type ◽  
Β Cell ◽  
Catalytic Function ◽  
Onset Diabetes ◽  
Impaired Insulin ◽  
Thermal Stability Of

The catalytic function and thermal stability of wild-type and mutant recombinant human pancreatic β-cell glucokinase was investigated. The mutants E70K and E300K, which are thought to be the cause of impaired insulin production by the pancreatic β-cell and decreased glucose uptake by the liver of patients with maturity-onset diabetes of the young, were found to be functionally indistinguishable from the wild-type, i.e. their kcat,S0.5, inflection point and hwere normal. However, these two mutants showed markedly reduced stability under a variety of test conditions. Glucokinase instability, not low enzyme catalytic activity, may be the cause of diabetes mellitus with E70K and E300K mutants.

scholarly journals Cell-biological assessment of human glucokinase mutants causing maturity-onset diabetes of the young type 2 (MODY-2) or glucokinase-linked hyperinsulinaemia (GK-HI)

1999 ◽  
Vol 342 (2) ◽  
pp. 345 ◽  
Author(s):  
Charlotte V. BURKE ◽  
Carol W. BUETTGER ◽  
Elizabeth A. DAVIS ◽  
Steven J. MCCLANE ◽  
Franz M. MATSCHINSKY ◽  
...  
Keyword(s):  
Biological Assessment ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

scholarly journals Childhood obesity complicating the differential diagnosis of maturity-onset diabetes of the young and type 2 diabetes

2007 ◽  
Vol 0 (0) ◽  
pp. 071127170524002-??? ◽  
Author(s):  
Naomi Weintrob ◽  
Eti Stern ◽  
Yaffa Klipper-Aurbach ◽  
Moshe Phillip ◽  
Galia Gat-Yablonski
Keyword(s):  
Type 2 Diabetes ◽  
Differential Diagnosis ◽  
Childhood Obesity ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

Common Variants in Maturity-Onset Diabetes of the Young Genes and Future Risk of Type 2 Diabetes

Diabetes ◽  
2008 ◽  
Vol 57 (6) ◽  
pp. 1738-1744 ◽  
Author(s):  
J. Holmkvist ◽  
P. Almgren ◽  
V. Lyssenko ◽  
C. M. Lindgren ◽  
K.-F. Eriksson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Maturity Onset Diabetes ◽  
Common Variants ◽  
Onset Diabetes ◽  
Future Risk

Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options

Endocrines ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 485-501
Author(s):  
Zoltan Antal
Keyword(s):  
Clinical Presentation ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Inappropriate Treatment ◽  
Monogenic Forms Of Diabetes ◽  
Initial Description

Maturity Onset Diabetes of the Young (MODY) encompasses a group of rare monogenic forms of diabetes distinct in etiology and clinical presentation from the more common forms of Type 1 (autoimmune) and Type 2 diabetes. Since its initial description as a clinical entity nearly 50 years ago, the underlying genetic basis for the various forms of MODY has been increasingly better elucidated. Clinically, the diagnosis may be made in childhood or young adulthood and can present as overt hyperglycemia requiring insulin therapy or as a subtle form of slowly progressive glucose impairment. Due to the heterogeneity of clinical symptoms, patients with MODY may be misdiagnosed as possessing another form of diabetes, resulting in potentially inappropriate treatment and delays in screening of affected family members and associated comorbidities. In this review, we highlight the various known genetic mutations associated with MODY, clinical presentation, indications for testing, and the treatment options available.

Functional characterization of two novel splicing mutations of glucokinase gene associated with maturity-onset diabetes of the young type 2 (MODY2)

2014 ◽  
Vol 48 (2) ◽  
pp. 248-253 ◽  
Author(s):  
E. L. Igudin ◽  
P. V. Spirin ◽  
V. S. Prasolov ◽  
N. A. Zubkova ◽  
E. E. Petryaikina ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Maturity Onset Diabetes ◽  
Glucokinase Gene ◽  
Splicing Mutations ◽  
Onset Diabetes

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Sebahat Yılmaz Ağladıoğlu ◽  
Zehra Aycan ◽  
Semra Çetinkaya ◽  
Veysel Nijat Baş ◽  
Aşan Önder ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Next Generation Sequencing ◽  
Point Mutations ◽  
Maturity Onset Diabetes ◽  
Turkish Children ◽  
Onset Diabetes ◽  
Molecular Studies ◽  
Generation Sequencing

AbstractMaturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11A panel of 11We identified 28 (65%) point mutations among 43 patients. Eighteen patients haveThis is the first study including molecular studies of 11

Characterization of glucokinase mutations associated with maturity-onset diabetes of the young type 2 (MODY-2): different glucokinase defects lead to a common phenotype

Diabetes ◽  
1999 ◽  
Vol 48 (8) ◽  
pp. 1645-1651 ◽  
Author(s):  
S. P. Miller ◽  
G. R. Anand ◽  
E. J. Karschnia ◽  
G. I. Bell ◽  
D. C. LaPorte ◽  
...  
Keyword(s):  
Maturity Onset Diabetes ◽  
Common Phenotype ◽  
Onset Diabetes ◽  
Glucokinase Mutations
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