Abstract
ABSTRACT Glucokinase (GK) is essential for glucose-stimulated insulin release from pancreatic β-cell, serving as glucose sensor in humans. Inactivating or activating mutations of glucokinase lead to different forms of “Glucokinase Disease”, i.e. Monogenic Diabetes of Youth (GCK-MDY), Permanent Neonatal Diabetes (inactivating mutations) and Congenital Hyperinsulinism, respectively. Here we present a novel GCK activating mutation (p.E442K) found in an infant with neonatal hypoglycemia (1.5 mmol/l) and in two other family members suffering from recurrent hypoglycemic episodes in their childhood and adult life. In contrast to the severe clinical presentation in the index case, functional studies showed only a slight activation of the protein (relative activity index of 3.3). We also report on functional studies of two inactivating mutations of the GCK (p.E440G and p.S441W), contiguous to the activating one, that lead to GCK-MDY. Interestingly, adult family members carrying the GCK pE440G mutation show an unusually “heterogeneous and progressive” diabetic phenotype, a feature not typical of MDY. In summary, we identified a novel activating GCK mutation that although being associated with severe neonatal hypoglycemia is characterized by the mildest activation of the glucokinase enzyme of all previously reported.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.