| Reference : Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and g... |
| Scientific journals : Article | |||
| Human health sciences : Multidisciplinary, general & others | |||
| http://hdl.handle.net/10993/27193 | |||
| Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes | |
| English | |
| Nielsen, L. B. [Department of Paediatrics, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600 Glostrup, Denmark] | |
| Ploug, K. B. [Department of Neurology, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600 Glostrup, Denmark] | |
| Swift, P. [Leicester Royal Infirmary Children's Hospital, Leicester, United Kingdom] | |
| Ørskov, C. [Department of Medical Anatomy, The Panum Institute, Copenhagen, Denmark] | |
| Jansen-Olesen, I. [Department of Neurology, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600 Glostrup, Denmark] | |
| Chiarelli, F. [Paediatric University Clinic, Chieti, Italy] | |
| Holst, J. J. [Department of Medical Physiology, The Panum Institute, Copenhagen, Denmark] | |
| Hougaard, P. [Department of Statistics, University of Southern Denmark, Odense, Denmark] | |
| Pörksen, S. [Department of Paediatrics, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600 Glostrup, Denmark] | |
| Holl, R. [The University of Ulm, Ulm, Germany] | |
De Beaufort, Carine  [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >] | |
| Gammeltoft, S. [Department of Clinical Biochemistry, Glostrup University Hospital, Glostrup, Denmark] | |
| Rorsman, P. [OCDEM, University of Oxford, Oxford OX3 7LJ, United Kingdom] | |
| Mortensen, H. B. [Department of Paediatrics, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600 Glostrup, Denmark] | |
| Hansen, L. [Development Projects, Novo Nordisk A/S, Bagsvœrd, Denmark] | |
| 2007 | |
| European Journal of Endocrinology | |
| 156 | |
| 6 | |
| 663-671 | |
| Yes (verified by ORBilu) | |
| 08044643 | |
| [en] C peptide ; L cell ; Western blotting ; Adolescent ; ATP-Binding Cassette Transporters ; Blotting, Western ; C-Peptide ; Child ; Diabetes Mellitus, Type 1 ; Eating ; Female ; Gastric Inhibitory Polypeptide ; Genotype ; Glucagon ; Glucagon-Like Peptide 1 ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Hypoglycemic Agents ; Ileum ; Immunohistochemistry ; Insulin ; Islets of Langerhans ; Male ; Polymorphism, Restriction Fragment Length ; Potassium Channels ; Potassium Channels, Inwardly Rectifying ; Receptors, Drug | |
| [en] Objective: The ATP-dependent K+-channel (KATP) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine α- and β-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the KATP channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu2Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes. Design and methods: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism. Results: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1c at diagnosis (coefficient= 0.61%, P= 0.02) and 1 month after initial insulin therapy (coefficient= 0.30%, P=0.05), but later disappeared. However, when adjusting HbA1c for the given dose of exogenous insulin, the dose-adjusted HbA1c remained higher throughout the 12 month study period (coefficient= 0.42%, P=0.03). Conclusions: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu2Lys variant of the KATP channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes. © 2007 Society of the European Journal of Endocrinology. | |
| http://hdl.handle.net/10993/27193 | |
| 10.1530/EJE-06-0756 |
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