Pathology
inactivating ABCC8 mutations in KATP channel-associated congenital hyperinsulinism
rare activating ABCC8 mutations in autosomal dominant diabetes (12559865)
Functional study of mutations
| Mutation | Functional alteration | Reference |
| DeltaF1388 | altered trafficking | - |
| A1457T | altered trafficking | - |
| V1550D | altered trafficking | - |
| L1551V | reduced surface expression | increased channel open probability |
Sur1 gene inactivation in mouse
In congenital hyperinsulinism of infancy (CHI), the loss of K-ATP channels (composed of Kir6.2 and SUR1 subunits) in beta cells induces permanent insulin secretion and severe hypoglycaemia. By contrast, Sur1 ( -/- ) mice do not present such defects.
The islets of Sur1 ( -/- ) mice present morphological modifications that have not been described in CHI and that might reflect an adaptive mechanism controlling insulin secretion in these mice. (19142666)
References
Impact of Sur1 gene inactivation on the morphology of mouse pancreatic endocrine tissue. Marhfour I, Moulin P, Marchandise J, Rahier J, Sempoux C, Guiot Y. Cell Tissue Res. 2009 Mar;335(3):505-15. PMID: 19142666
Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL, Ellard S. Hum Mutat. 2009 Feb;30(2):170-80. PMID: 18767144
Ellard S, Flanagan SE, Girard CA, Patch AM, Harries LW, Parrish A, Edghill EL, Mackay DJ, Proks P, Shimomura K, Haberland H, Carson DJ, Shield JP, Hattersley AT, Ashcroft FM. Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. Am J Hum Genet. 2007 Aug;81(2):375-82. PMID: 17668386
Huopio H, Shyng SL, Otonkoski T, Nichols CG. K(ATP) channels and insulin secretion disorders. Am J Physiol Endocrinol Metab. 2002 Aug;283(2):E207-16. PMID: 12110524