ArticleDiabetologia2021
The novel GCK variant p.Val455Leu associated with hyperinsulinism is susceptible to allosteric activation and is conducive to weight gain and the development of diabetes.
Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes.Nature genetics · 2024Pooled it
- Modelling the effects of human SUR1 R1420H variation on insulin secretory function using isogenic iPSC-derived pancreatic islets.Diabetologia · 2026Article
- Functional Characterization of Glucokinase Variants to Aid Clinical Interpretation of Monogenic Diabetes.International journal of molecular sciences · 2025Article
- Genotype-histotype-phenotype correlations in hyperinsulinemic hypoglycemia.Histology and histopathology · 2024Review
- Recent drug development of dorzagliatin, a new glucokinase activator, with the potential to treat Type 2 diabetes: A review study.Journal of diabetes · 2024Review
- Whole-exome sequencing reveals novel variants of monogenic diabetes in Tunisia: impact on diagnosis and healthcare management.Frontiers in genetics · 2023Article
- From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.Frontiers in endocrinology · 2023Review
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
- Stem Cell Based Models in Congenital Hyperinsulinism - Perspective on Practicalities and Possibilities.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe mammalian enzyme glucokinase (GK), expressed predominantly in liver and pancreas, plays an essential role in carbohydrate metabolism. Monogenic GK disorders emphasise the role of GK in determining the blood glucose set point.
methodsA family with congenital hyperinsulinism (CHI) was examined for GCK gene variants by Sanger sequencing. A combined approach, involving kinetic analysis (also using GK activators and inhibitors), intracellular translocation assays, insulin secretion measurements and structural modelling, was used to investigate the novel variant compared with known variants.
resultsWe report on the novel gain-of-function GCK variant p.Val455Leu (V455L), inherited as an autosomal dominant trait in a German family with CHI and concomitant obesity (fasting blood glucose 2.1 mmol/l, BMI 45.0 kg/m CONCLUSION/
interpretationWe provide new knowledge on the structure-function relationship of GK, with special emphasis on enzyme activation, potentially yielding fresh strategic insights into breaking the vicious circle of fluctuating blood glucose levels and the attendant risk of long-lasting metabolic changes in both CHI and type 2 diabetes.
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