Functional characterization of activating mutations in the sulfonylurea receptor 1 ( ABCC8 ) causing neonatal diabetes mellitus in Asian Indian children

2019 ◽  
Vol 20 (4) ◽  
pp. 397-407 ◽  
Author(s):  
Kandasamy Balamurugan ◽  
Babu Kavitha ◽  
Zhongying Yang ◽  
Viswanathan Mohan ◽  
Venkatesan Radha ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Asian Indian ◽  
Functional Characterization ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Sulfonylurea Receptor ◽  
Indian Children ◽  
Activating Mutations ◽  
Sulfonylurea Receptor 1

Four novel splice variants of sulfonylurea receptor 1

2002 ◽  
Vol 283 (2) ◽  
pp. C587-C598 ◽  
Author(s):  
Annette Hambrock ◽  
Regina Preisig-Müller ◽  
Ulrich Russ ◽  
Anke Piehl ◽  
Peter J. Hanley ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Splice Variants ◽  
Functional Characterization ◽  
Pcr Analysis ◽  
Sulfonylurea Receptor ◽  
Transmembrane Segments ◽  
Sulfonylurea Receptor 1 ◽  
Green Fluorescent ◽  
Splice Forms

ATP-sensitive K+ (KATP) channels are composed of pore-forming Kir6.x subunits and regulatory sulfonylurea receptor (SUR) subunits. SURs are ATP-binding cassette proteins with two nucleotide-binding folds (NBFs) and binding sites for sulfonylureas, like glibenclamide, and for channel openers. Here we report the identification and functional characterization of four novel splice forms of guinea pig SUR1. Three splice forms originate from alternative splicing of the region coding for NBF1 and lack exons 17 (SUR1Δ17), 19 (SUR1Δ19), or both (SUR1Δ17Δ19). The fourth (SUR1C) is a COOH-terminal SUR1-fragment formed by exons 31–39 containing the last two transmembrane segments and the COOH terminus of SUR1. RT-PCR analysis showed that these splice forms are expressed in several tissues with strong expression of SUR1C in cardiomyocytes. Confocal microscopy using enhanced green fluorescent protein-tagged SUR or Kir6.x did not provide any evidence for involvement of these splice forms in the mitochondrial KATP channel. Only SUR1 and SUR1Δ17 showed high-affinity binding of glibenclamide ( K d≈ 2 nM in the presence of 1 mM ATP) and formed functional KATPchannels upon coexpression with Kir6.2.

Clinical and molecular characterization of neonatal diabetes and monogenic syndromic diabetes in Asian Indian children

2012 ◽  
Vol 83 (5) ◽  
pp. 439-445 ◽  
Author(s):  
S Jahnavi ◽  
V Poovazhagi ◽  
V Mohan ◽  
D Bodhini ◽  
P Raghupathy ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Asian Indian ◽  
Neonatal Diabetes ◽  
Indian Children

EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome

2013 ◽  
Vol 15 (4) ◽  
pp. 313-318 ◽  
Author(s):  
Suresh Jahnavi ◽  
Varadarajan Poovazhagi ◽  
Sekar Kanthimathi ◽  
Vijay Gayathri ◽  
Viswanathan Mohan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Indian Children ◽  
Permanent Neonatal Diabetes ◽  
Permanent Neonatal Diabetes Mellitus ◽  
South Indian

scholarly journals A case with relapsed transient neonatal diabetes mellitus treated with sulfonylurea, ending chronic insulin requirement

2018 ◽  
Vol 2018 ◽  
Author(s):  
Akihiko Ando ◽  
Shoichiro Nagasaka ◽  
Shun Ishibashi
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Testing ◽  
Glycaemic Control ◽  
Genetic Defect ◽  
Neonatal Diabetes ◽  
Insulin Requirement ◽  
Neonatal Diabetes Mellitus ◽  
List Type ◽  
Sulfonylurea Receptor ◽  
Early Screening

Summary We report a case of a woman with diabetes mellitus caused by a genetic defect in ABCC8-coding sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium (KATP) channel protein. She was diagnosed with diabetes at 7 days after birth. After intravenous insulin drip for 1 month, her hyperglycaemia remitted. At the age of 13 years, her diabetes relapsed, and after that she had been treated by intensive insulin therapy for 25 years with relatively poor glycaemic control. She was switched to oral sulfonylurea therapy and attained euglycaemia. In addition, her insulin secretory capacity was ameliorated gradually. Learning points: Genetic testing should be considered in any individuals or family with diabetes that occurred within the first year or so of life. Sulfonylurea can achieve good glycaemic control in patients with KATP channel mutations by restoring endogenous insulin secretion, even if they were treated with insulin for decades. Early screening and genetic testing are important to improve the prognosis of patients with neonatal diabetes mellitus arising from ABCC8 or KCNJ11 mutation.

scholarly journals Characterization of the Methylation-sensitive Promoter of the ImprintedZACGene Supports Its Role in Transient Neonatal Diabetes Mellitus

2001 ◽  
Vol 276 (22) ◽  
pp. 18653-18656 ◽  
Author(s):  
Annie Varrault ◽  
Benoit Bilanges ◽  
Deborah J. G. Mackay ◽  
Eugenia Basyuk ◽  
Barbara Ahr ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Transient Neonatal Diabetes Mellitus ◽  
Transient Neonatal Diabetes

scholarly journals Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene

2008 ◽  
Vol 52 (8) ◽  
pp. 1350-1355 ◽  
Author(s):  
Thais Della Manna ◽  
Claudilene Battistim ◽  
Vanessa Radonsky ◽  
Roberta D. Savoldelli ◽  
Durval Damiani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hemoglobin A1c ◽  
Neonatal Diabetes ◽  
Tolerance Test ◽  
Neonatal Diabetes Mellitus ◽  
Oral Glucose ◽  
Permanent Neonatal Diabetes ◽  
Permanent Neonatal Diabetes Mellitus ◽  
Activating Mutations ◽  
Brazilian Child

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.

Activating Mutations in theABCC8Gene in Neonatal Diabetes Mellitus

2006 ◽  
Vol 355 (5) ◽  
pp. 456-466 ◽  
Author(s):  
Andrey P. Babenko ◽  
Michel Polak ◽  
Hélène Cavé ◽  
Kanetee Busiah ◽  
Paul Czernichow ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Activating Mutations
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