Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11

Edghill, Emma L.; Flanagan, Sarah E.; Ellard, Sian

doi:10.1007/s11154-010-9149-x

Cited by 80 publications

(76 citation statements)

References 61 publications

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“…Therefore, they have an overactive channel that remains opened, either increasing the K ATP activity mediated by Mg nucleotides or altering the intrinsic gating (Edghill et al, 2010;Remedi and Koster, 2010). Gloyn et al (2004) reported genetic variants in Kir6.2 as the potential cause of NDM for the first time in 2004.…”

Section: Pancreatic K Atp Channelopathiesmentioning

confidence: 99%

“…In addition, variants of Val59, Cys166, Ile197, and Ile296 residues involved in the channel gating impair the open probability of the channel (Proks et al, 2005;Edghill et al, 2010). SUR1 mutations affect either the Mg-nucleotide-mediated activation or the intrinsic gating.…”

Section: Pancreatic K Atp Channelopathiesmentioning

confidence: 99%

“…SUR1 mutations affect either the Mg-nucleotide-mediated activation or the intrinsic gating. These mutations could be located along the protein length, including many instances of the following amino acid substitutions V1523A, V1524M, I1425V, and R1531A in NBD2 (Edghill et al, 2010).…”

Section: Pancreatic K Atp Channelopathiesmentioning

confidence: 99%

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Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Velasco

Díaz‐García

Larqué

et al. 2016

Molecular Pharmacology

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Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (K ATP ) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na 1 channels (Nav) and subsequently voltage-dependent Ca 21 channels (Cav).The increase in intracellular Ca 21 triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (K ATP , Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion.

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Section: Pancreatic K Atp Channelopathiesmentioning

confidence: 99%

Section: Pancreatic K Atp Channelopathiesmentioning

confidence: 99%

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Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Velasco

Díaz‐García

Larqué

et al. 2016

Molecular Pharmacology

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“…Olguların çoğunun SUR1 (ABCC8) genindeki mutasyonlardan kaynaklandığı bildirilmiş ve bugüne kadar 150'den fazla mutasyon tespit edilmiştir (9,10) . Daha az oranda ise Kir.…”

Section: Discussionunclassified

A Neonatal Case of Congenital Hyperinsulinism Due to Homozygous KCNJ11 Gene Mutation

Demirol¹,

Olukman²,

Elmas³

et al. 2017

Terh

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ÖZKonjenital hiperinsülinizm (KHİ), yenidoğan ve erken infantil dönemde yineleyici veya inatçı ağır hipogliseminin en sık nedenlerinden birisidir. Hastalığın görülme sıklığı toplumlar arasında farklılık göstermekle birlikte, genel populasyondaki sporadik oranlar yaklaşık 40000-50000 canlı doğumda birdir. Araplar, Ashkenazi Yahudileri ve Türkler gibi akraba evliliklerinin yaygın olduğu toplumlarda hastalığın ailesel formlarının görülme oranı 2500 canlı doğumda bire kadar yükselebilir. Etiyolojide sıklıkla pankreatik beta hücrelerinden insülin salınımında rol alan yolaklardaki genetik bozukluklar sorumlu tutulmaktadır. Ancak bugüne dek tanımlanabilen mutasyonların oranı hemen hemen %50 düzeyindedir. KHİ'de en yaygın rastlanan genetik defekt, K+ATP kanallarını oluşturan SUR1 ve Kir. 6,2'yi kodlayan, 11. kromozomda lokalize ABCC8 ve KCNJ11 gen mutasyonlarıdır. Bu makalede homozigot KCNJ11 gen mutasyonuna bağlı KHİ tanısı konulan bir yenidoğan olgusu, hastalığın inatçı ağır neonatal hipogliseminin ayırıcı tanısında önemini vurgulamak ve yüklü aile öyküsü varlığında ileri genetik çalışmaların gerekliliğine dikkat çekmek amacıyla sunulmuş-tur.Anahtar kelimeler: Konjenital hiperinsülinizm, KCNJ11 gen mutasyonu, olgu sunumu ABSTRACT Congenital hyperinsulinism (CHI) is one of the most common causes of recurrent or persistent severe hypoglycemia in the neonatal period and early infancy. Although the incidence may vary widely among different populations, the sporadic rates in the general population is approximately 1/40,000-50,000 live births. The incidence of the familial forms may be as high as 1/2,500 in certain communities like Arabs, Ashkenazi Jews and Turks, in which consanguineous marriages are common. Genetic disorders of the pathways of insulin release from pancreatic beta cells are frequently held responsible for the etiology. However the incidence rate of the identified mutations up to date is nearly 50 percent. The most common genetic defects found in CHI are mutations in the ABCCS and KCNJ11 genes, which are located on chromosome 11p and encode for the SUR1 and Kir 6.2 subunits of the KATP channels. Here we report a newborn infant diagnosed as CHI due to homozygous KCNJ11 gene mutation with the aim of emphasizing the importance of CHI in the differential diagnosis of persistent neonatal hypoglycemia and attracting attention to the necessity of further genetic studies in the presence of strong familial history.

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“…Many of these genes have also been described in other disorders of insulin secretion, namely neonatal diabetes or congenital hyperinsulinism [43][44][45][46]. MODY 2 (GCK) and MODY 3 (HNF1A) account for the majority of MODY [18,20].…”

Section: Subtypes Of Modymentioning

confidence: 99%

Monogenic disorders of glucose-stimulated insulin secretion: massively parallel sequencing approaches

Johnson¹

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Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11

Cited by 80 publications

References 61 publications

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

A Neonatal Case of Congenital Hyperinsulinism Due to Homozygous KCNJ11 Gene Mutation

Monogenic disorders of glucose-stimulated insulin secretion: massively parallel sequencing approaches

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