References of "Rorsman, P."
     in
Bookmark and Share    
Peer Reviewed
See detailCo-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
Nielsen, L. B.; Ploug, K. B.; Swift, P. et al

in European Journal of Endocrinology (2007), 156(6), 663-671

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 97 (0 UL)