We studied 86 adult offspring (mean age 40 years), 49 born to glucokinase mothers (exposed to hyperglycaemia in utero) and 37 born to glucokinase fathers (controls).
Moreover, an additive effect of GCKR rs1260326(T) and GCK (-30G) alleles conferred lower fasting glycemia (P = 1 x 10(-13)), insulinemia (P = 5 x 10(-6)), and hyperglycemia risk (P = 1 x 10(-6)).
This nonradioactive SSCP technique may be useful to routinely diagnose glucokinase deficiency, which is an important cause of hyperglycemia among young type II diabetic patients.
In pregnancies where the mother has hyperglycemia due to a GCK mutation, knowing the fetal GCK genotype guides the management of maternal hyperglycemia.
Functional studies of naturally occurring GCK mutations associated with hyperglycaemia provide further insight into the biochemical basis of glucose sensor regulation.
Mutants of glucokinase cause hypoglycaemia- and hyperglycaemia syndromes and their analysis illuminates fundamental quantitative concepts of glucose homeostasis.
The findings leading to the diagnosis were impaired fasting glucose (IFG) (15/37), symptoms of hyperglycemia (4/37), and a GCK-MODY family history (18/37).
The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations.
Mutations in glucokinase/MODY2 result in mild chronic hyperglycaemia due to reduced pancreatic beta-cell responsiveness to glucose as well as decreased net accumulation of hepatic glycogen and increased hepatic gluconeogenesis following meals.
Our findings link defects in hormone-regulated GCK S-nitrosylation to hyperglycemia and support a role for posttranslational regulation of GCK S-nitrosylation as a vital regulatory mechanism for glucose-stimulated insulin secretion.