Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea.

  title={Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea.},
  author={E. Lau and C. Correia and P. Freitas and C. Nogueira and M. Costa and A. Saavedra and C. Costa and D. Carvalho and M. Fontoura},
  journal={Archives of endocrinology and metabolism},
  volume={59 6},
Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val… Expand
Neonatal diabetes due to potassium channel mutation: response to sulfonylurea according to the genotype.
Sulfonylurea are an effective treatment for monogenic diabetes due to KCNJ11 and ABCC8 genes mutations and the success of the treatment is conditioned by differences in pharmacogenetics, younger age, pharmacokinetics, compliance and maximal dose used. Expand
KATP Channel Mutations and Neonatal Diabetes
This review focuses on mutations of Kir6.2, the pore-forming subunit and sulfonylurea receptor (SUR) 1, the regulatory subunit of the KATP channel, which cause neonatal diabetes/DEND syndrome and also discusses the findings of the pathological mechanisms that are associated with Neonatal diabetes, and its neurological features. Expand
Channel Mutations and Neonatal Diabetes Kenju Shimomura and
Since the discovery of the KATP channel in 1983, numerous studies have revealed its physiological functions. The KATP channel is expressed in various organs, including the pancreas, brain andExpand
Recent Advances in Neonatal Diabetes
Patients with mutations of either KCNJ11 or ABCC8 that encode subunits of the KATP channel gene mutation can be managed with sulfonylurea oral therapy while patients with other genetic mutations require insulin treatment. Expand
Genetic Susceptibility to Transient and Permanent Neonatal Diabetes Mellitus
Mutation in the KCNJ11 and ABCC8 genes can cause both TNDM and PNDM, and infant with this mutation can respond to transition from insulin to sulfonylureas making identification of genes involved in the disease important for appropriate treatment. Expand
Permanent neonatal diabetes: combining sulfonylureas with insulin may be an effective treatment
The case of a woman with diabetes due to a KCNJ11 mutation, in whom combination therapy led to clinically meaningful improvements is presented. Expand
Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery
The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. Expand
Traitement par sulfamides hypoglycémiants dans le diabète néonatal : étude de l’efficacité thérapeutique selon le génotype puis utilisation dans le diabète néonatal transitoire par anomalie du chromosome 6
Contexte : le diabete neonatal (DN) peut etre du a des mutations de canaux potassiques ATP-dependants par mutation des genes KCNJ11 ou ABCC8. Les sulfamides hypoglycemiants (SU) peuvent traiter le DNExpand
DMSO_A_198932 355..364
Division of Pediatric Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Neonatal diabetes mellitus (DM) is defined by the onsetExpand


Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.
Apparently insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment. Expand
Perspectives in Diabetes Activating Mutations in Kir 6 . 2 and Neonatal Diabetes New Clinical Syndromes , New Scientific Insights , and New Therapy
Closure of ATP-sensitive K channels (KATP channels) in response to metabolically generated ATP or binding of sulfonylurea drugs stimulates insulin release from pancreatic -cells. HeterozygousExpand
Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2.
The feasibility of oral sulfonylurea treatment in PNDM patients with Kir6.2 mutations even during infancy is demonstrated, and the superiority of this approach over insulin administration is demonstrated. Expand
Relapsing diabetes can result from moderately activating mutations in KCNJ11.
Mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes, which suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. Expand
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations.
Sulfonylurea therapy is safe in the short term for patients with diabetes caused by KCNJ11 mutations and is probably more effective than insulin therapy, and may result from the closing of mutant K(ATP) channels, thereby increasing insulin secretion in response to incretins and glucose metabolism. Expand
Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.
It is found that mutations causing PNDM alone impair ATP sensitivity directly (at the binding site), whereas those associated with severe disease act indirectly by biasing the channel conformation toward the open state. Expand
Secondary consequences of beta cell inexcitability: identification and prevention in a murine model of K(ATP)-induced neonatal diabetes mellitus.
Transgenic mice carrying an ATP-insensitive mutant K(ATP) channel subunit prevented diabetes and secondary complications in mice but failed to halt disease progression after diabetes had developed, suggesting that transfer to sulfonylurea therapy is less effective in older patients. Expand
Neonatal diabetes mellitus: a disease linked to multiple mechanisms
Molecular analysis of chromosome 6 anomalies, and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period, and has potentially important therapeutic consequences leading to transfer some patients from insulin therapy to sulfonylureas. Expand
K(ATP) channels and insulin secretion: a key role in health and disease.
  • F. Ashcroft
  • Biology, Medicine
  • Biochemical Society transactions
  • 2006
This review summarizes advances in understanding of the structure and function of the ATP-sensitive potassium (K(ATP) channel of the pancreatic beta-cell that have been made over the last 5 years and illustrates how mouse models of glucose intolerance or diabetes can provide fresh insight into beta- cell function. Expand
Diagnosis and treatment of neonatal diabetes: an United States experience †
Background/objective:  Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a smallExpand