Heterozygous mutations in glucokinase (GCK) are associated with mild fasting hyperglycemia and gestational diabetes mellitus while homozygous or compound heterozygous GCK mutations result in permanent neonatal diabetes mellitus.
A novel glucokinase deletion (p.Lys32del) and five previously described mutations co-segregate with the phenotype of mild familial hyperglycaemia (MODY2) in Brazilian families.
The most frequently observed combinations of symptoms typical for GCK-MD were mild diabetes and/or fasting hyperglycaemia (98.3%), positive C-peptide at diagnosis (76%) and dominant mode of inheritance (59%).
We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes.
Identification of a novel beta-cell glucokinase (GCK) promoter mutation (-71G>C) that modulates GCK gene expression through loss of allele-specific Sp1 binding causing mild fasting hyperglycemia in humans.
We genetically analyzed four families of young children with fasting hyperglycemia with family histories of diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha (HNF4alpha), glucokinase (GCK), and hepatocyte nuclear factor 1 alpha (HNF1alpha), the genes responsible for MODY1, MODY2, and MODY3, respectively.
Rare mutations in the glucokinase (GCK) gene cause fasting hyperglycemia and considerably influence birth weight when present in a mother or her offspring.
We hypothesize that not all MODY 2 affected fetuses need the same levels of hyperglycemia to have an appropriate growth, maybe because different kinds of GCK mutations may result in different phenotypes.
We found that mice with deletion of the insulin receptor alone showed not only hyperglycemia but also a 70% decrease in plasma insulin-like growth factor 1 and delayed growth during the first 2 months of life, a 24-fold increase in the soluble leptin receptor and a 19-fold increase in plasma leptin levels.
The unique role of glucokinase in human glucose physiology is illustrated by the fact that genetic mutations in glucokinase can either cause hyperglycaemia or hypoglycaemia.
Caucasian gestational diabetic subjects from the United Kingdom who had fasting hyperglycaemia in pregnancy but did not meet the diagnostic criteria for maturity-onset diabetes of the young (MODY) were selected for direct sequencing of the glucokinase gene if they fulfilled the following four criteria; (1) persisting fasting hyperglycaemia outside pregnancy (5.5-8 mmol/l) (2) a small increment (< 4.6 mmol/l) during a 2-h oral glucose tolerance test (3) insulin treatment during at least one pregnancy but subsequently controlled on diet and (4) a history of Type II (non-insulin-dependent) diabetes mellitus, gestational diabetes or fasting hyperglycaemia (> 5.5 mmol/l) in a first-degree relative.
At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA<sub>1c</sub> <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY.
HNF-1alpha gene mutations (MODY3) present with marked hyperglycemia in lean young adults and may, therefore, be mistaken for type 1 diabetes, with implications for individual treatment and risk of diabetes in other family members.
Moreover, compared with control group the expression of IL1R1 and IL-6 genes both were downregulated in individuals with moderately high blood glucose levels by 2.38 (p = 0.0365) and 4.34 fold (p = 0.0027), respectively.
We investigated the natural history of glucokinase (GCK)-related maturity-onset diabetes of the young type 2 (MODY2), notably the factors associated with deterioration of hyperglycemia over time.