A Kir6.2 mutation causing severe functional effects in vitro produces neonatal diabetes without the expected neurological complications.

ABSTRACT:

Aims/hypothesis

Heterozygous activating mutations in the pancreatic ATP-sensitive K+ channel cause permanent neonatal diabetes mellitus (PNDM). This results from a decrease in the ability of ATP to close the channel, which thereby suppresses insulin secretion. PNDM mutations that cause a severe reduction in ATP inhibition may produce additional symptoms such as developmental delay and epilepsy. We identified a heterozygous mutation (L164P) in the pore-forming (Kir6.2) subunit of the channel in three unrelated patients and examined its functional effects.

Methods

The patients (currently aged 2, 8 and 20 years) developed diabetes shortly after birth. The two younger patients attempted transfer to sulfonylurea therapy but were unsuccessful (up to 1.1 mg kg(-1) day(-1)). They re

SUBMITTER: Tammaro P 

PROVIDER: S-EPMC2292422 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature