The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism
Congenital hyperinsulinism (CHI) is a heterogenous and complex disorder in which the unregulated insulin secretion from pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia. The severity of hypoglycaemia varies depending on the underlying molecular mechanism and genetic defects. The geneti...
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doaj-222e769b25474ae48c1b60fdb8a0d9f72020-11-24T21:00:31ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-02-011010.3389/fendo.2019.00111434796The Genetic and Molecular Mechanisms of Congenital HyperinsulinismSonya Galcheva0Hüseyin Demirbilek1Sara Al-Khawaga2Khalid Hussain3Department of Paediatrics, University Hospital St. Marina, Varna Medical University, Varna, BulgariaDepartment of Paediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, TurkeyDivision of Endocrinology, Department of Paediatric Medicine, Sidra Medicine, Doha, QatarDivision of Endocrinology, Department of Paediatric Medicine, Sidra Medicine, Doha, QatarCongenital hyperinsulinism (CHI) is a heterogenous and complex disorder in which the unregulated insulin secretion from pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia. The severity of hypoglycaemia varies depending on the underlying molecular mechanism and genetic defects. The genetic and molecular causes of CHI include defects in pivotal pathways regulating the secretion of insulin from the beta-cell. Broadly these genetic defects leading to unregulated insulin secretion can be grouped into four main categories. The first group consists of defects in the pancreatic KATP channel genes (ABCC8 and KCNJ11). The second and third categories of conditions are enzymatic defects (such as GDH, GCK, HADH) and defects in transcription factors (for example HNF1α, HNF4α) leading to changes in nutrient flux into metabolic pathways which converge on insulin secretion. Lastly, a large number of genetic syndromes are now linked to hyperinsulinaemic hypoglycaemia. As the molecular and genetic basis of CHI has expanded over the last few years, this review aims to provide an up-to-date knowledge on the genetic causes of CHI.https://www.frontiersin.org/article/10.3389/fendo.2019.00111/fullhyperinsulinismhypoglycaemiamolecular mechanismsgeneticsmutation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sonya Galcheva Hüseyin Demirbilek Sara Al-Khawaga Khalid Hussain |
spellingShingle |
Sonya Galcheva Hüseyin Demirbilek Sara Al-Khawaga Khalid Hussain The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism Frontiers in Endocrinology hyperinsulinism hypoglycaemia molecular mechanisms genetics mutation |
author_facet |
Sonya Galcheva Hüseyin Demirbilek Sara Al-Khawaga Khalid Hussain |
author_sort |
Sonya Galcheva |
title |
The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism |
title_short |
The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism |
title_full |
The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism |
title_fullStr |
The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism |
title_full_unstemmed |
The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism |
title_sort |
genetic and molecular mechanisms of congenital hyperinsulinism |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2019-02-01 |
description |
Congenital hyperinsulinism (CHI) is a heterogenous and complex disorder in which the unregulated insulin secretion from pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia. The severity of hypoglycaemia varies depending on the underlying molecular mechanism and genetic defects. The genetic and molecular causes of CHI include defects in pivotal pathways regulating the secretion of insulin from the beta-cell. Broadly these genetic defects leading to unregulated insulin secretion can be grouped into four main categories. The first group consists of defects in the pancreatic KATP channel genes (ABCC8 and KCNJ11). The second and third categories of conditions are enzymatic defects (such as GDH, GCK, HADH) and defects in transcription factors (for example HNF1α, HNF4α) leading to changes in nutrient flux into metabolic pathways which converge on insulin secretion. Lastly, a large number of genetic syndromes are now linked to hyperinsulinaemic hypoglycaemia. As the molecular and genetic basis of CHI has expanded over the last few years, this review aims to provide an up-to-date knowledge on the genetic causes of CHI. |
topic |
hyperinsulinism hypoglycaemia molecular mechanisms genetics mutation |
url |
https://www.frontiersin.org/article/10.3389/fendo.2019.00111/full |
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