ABCMdb

PMID: 12623163

Gribble FM, Reimann F
Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions.
J Diabetes Complications. 2003 Mar-Apr;17(2 Suppl):11-5., [PubMed]

Sentences

No. Mutations Sentence Comment

67 ABCC8 p.Ser1237Tyr The difference between SUR1 and SUR2 that accounts for the different sensitivities to KATP channel inhibitors has been localised to the TM15-16 loop, in which a single amino acid substitution (S1237Y) in SUR1 is sufficient to abolish the action of tolbutamide on channel activity and to prevent binding of [3 H]glibenclamide (Ashfield et al., 1999). Login to comment 69 ABCC8 p.Ser1237Tyr The actions of meglitinide and repaglinide on Kir6.2/SUR1 currents are not affected by the S1237Y mutation (Ashfield et al., 1999; Dabrowski et al., 2001), supporting the idea that a different region of the binding site (e.g., the TMs 5-6 loop) is involved. Login to comment 71 ABCC8 p.Ser1237Tyr Inability to bind to the TMs 15-16 loop, either in SUR2 or SUR1-S1237Y, accounts for the rapid reversibility of glibenclamide and glimepiride in these cases. Login to comment 72 ABCC8 p.Ser1237Tyr The slow reversibility of repaglinide cannot be explained on the same basis, as it is unaffected by the SUR type or the S1237Y mutation in SUR1, and is likely to be attributable to its greater hydrophobicity. Login to comment