ABCMdb

PMID: 12819907

Gribble FM, Reimann F
Sulphonylurea action revisited: the post-cloning era.
Diabetologia. 2003 Jul;46(7):875-91. Epub 2003 Jun 18., [PubMed]

Sentences

No. Mutations Sentence Comment

69 ABCC8 p.Glu1506Lys A mutation in SUR1 (E1506K) that causes mild autosomal dominant CHI in infants, has also been found to cause autosomal dominant Type 2 diabetes in adult life [78, 79]. Login to comment 130 ABCC8 p.Ser1237Tyr The binding site for sulphonylureas and glinides could therefore be envisaged as a pocket with at least two binding motifs, one (exclusive to SUR1 and abolished by the S1237Y mutation) favouring sulphonylurea groups, and the other (common to SUR1 and SUR2) preferring meglitinide-like molecules [4, 44, 91]. Login to comment 135 ABCC8 p.Ser1237Tyr In line with this idea, mutation of S1237Y in SUR1 increased glibenclamide reversibility in patch clamp experiments and impaired the binding of [3H]glibenclamide [49, 91], whereas the reverse mutation (Y1206S) in SUR2B increased the [3H]glibenclamide binding affinity [92]. Login to comment 136 ABCC8 p.Ser1237Tyr Neither repaglinide reversibility, nor binding of [3H]repaglinide, were affected by the S1237Y mutation in SUR1 [47, 49]. Login to comment 154 ABCC8 p.Ser1237Tyr Thus, they both inhibited Kir6.2/SUR1 with higher affinity than Kir6.2/SUR2 currents, and inhibition of SUR1-type channels was impaired by the S1237Y mutation [48, 49, 50, 97]. Login to comment