ABCC8 genetic variants and risk of diabetes mellitus

Haghverdizadeh, Polin; Haerian, Monir Sadat; Haghverdizadeh, Pantea; Haerian, Batoul Sadat

doi:10.1016/j.gene.2014.04.040

Cited by 36 publications

(27 citation statements)

References 48 publications

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“…Mutations in ABCC8 are associated with MODY, type 2 diabetes and gestational diabetes. Some mutations in ABCC8 cause hyperinsulinemia in newborns [16, 17]. Besides, some ABCC8 mutations were revealed in subjects with neonatal diabetes [18–20].…”

Section: Discussionmentioning

confidence: 99%

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

et al. 2016

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Maturity-onset diabetes of the young (MODY) is a heterogeneous group of diseases associated with gene mutations leading to dysfunction of pancreatic β-cells. Thirteen identified MODY variants differ from each other by the clinical course and treatment requirement. Currently, MODY subtypes 1–5 are best-studied, descriptions of the other forms are sporadic. This article reports a MODY12 clinical case, caused by a mutation in the gene of the ATP-binding cassette transporter sub-family C member 8 (ABCC8), encoding sulfonylurea receptor 1. Diabetes manifested in a 27-year-old non-obese man with epilepsy in anamnesis. No evidence of ketosis was present, pancreatic antibodies were undetectable, and C-peptide remained within the reference range. During the initial investigation, non-proliferative diabetic retinopathy and elevated albumin excretion rate was revealed. After 4 months, diabetes was complicated by pre-proliferative retinopathy and diabetic macular edema. Recurrent hypoglycemia and an increase in body weight was observed on moderate and even small insulin doses. Taking into account the clinical features and the presence of diabetes in four generations on the maternal side, screening for all MODY subtypes was performed. A mutation in the ABCC8 gene was found in proband and in his mother. After the insulin discontinuation, gliclazide modified release combined with sodium/glucose cotransporter 2 (SGLT2) inhibitors was started. This treatment eliminated hypoglycemia and improved glycemic variability parameters. A decrease in the amplitude of glucose excursions was documented by continuous glucose monitoring. After 3 months of treatment, glycemic control was still optimal, and no hypoglycemic episodes were observed. The case report demonstrates the clinical features of ABCC8-associated MODY and the therapeutic potential of a combination of sulfonylurea with SGLT2 inhibitor in this disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0192-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

et al. 2016

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“…After exclusion of medications with more than two annotated targets, we advanced for analysis only genes (a) annotated as a target of at least two compounds and (b) for which the therapeutic target modulation strategy was consistently annotated across all medications, where annotations of “inhibitor”, “antagonist”, and “inverse agonist” were interpreted as reducing activity, while annotations of “agonist”, “activator”, or “inducer” were interpreted as increasing activity. These restrictions excluded ABCC8 from analysis, as it was annotated as the target of both an inhibitor and an agonist; we elected to maintain this exclusion, despite multiple lines of evidence 109 indicating inhibition of ABCC8 to be the appropriate anti-diabetic strategy, to maintain consistent criteria across all genes selected for analysis. Additionally, we excluded KCNJ11 (which with ABCC8 encodes the ATP-sensitive K(ATP) channel targeted by sulfonylureas) from analysis because both medications listed in DrugBank as targeting it had more than two targets (Glyburide, 8, and Glimepiride, 3).…”

Section: Methodsmentioning

confidence: 99%

Genetic discovery and translational decision support from exome sequencing of 20,791 type 2 diabetes cases and 24,440 controls from five ancestries

Flannick¹,

Jm²,

Fuchsberger³

et al. 2018

Preprint

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“…ABCC8 is considered to be more highly expressed in the human brain than ABCC9 (Shi, et al, 2005), and ABCC8 /SUR1 has been implicated in neuropathologic processes (Jiang, et al, 2007,Mehta, et al, 2013,Simard, et al, 2008a,Simard, et al, 2008b,Simard, et al, 2012,Tosun, et al, 2013). Mutations in ABCC8 are associated with congenital hyperinsulinism and diabetes (Bonfanti, et al, 2015,Bryan, et al, 2007,Efferth, 2003,Haghverdizadeh, et al, 2014,Remedi and Nichols, 2009,Smith, et al, 2007). In the latter case, more severe mutations are associated with a complex syndrome (Developmental delay, Epilepsy and Neonatal diabetes, DEND), in which CNS excitability is aberrant, as a result of hyperactivity of the SUR1-regulated K ATP channel activity.…”

Section: Abcc Genetic Phylogeny and The Role Of Abcc9 Paralogs In Hummentioning

confidence: 99%

ABCC9/SUR2 in the brain: Implications for hippocampal sclerosis of aging and a potential therapeutic target

Nelson

Jicha

Wang

et al. 2015

Ageing Research Reviews

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The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“KATP”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a “druggable target”, relevant perhaps to both HS-Aging and Alzheimer’s disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions.

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ABCC8 genetic variants and risk of diabetes mellitus

Cited by 36 publications

References 48 publications

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective

Genetic discovery and translational decision support from exome sequencing of 20,791 type 2 diabetes cases and 24,440 controls from five ancestries

ABCC9/SUR2 in the brain: Implications for hippocampal sclerosis of aging and a potential therapeutic target

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