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A human pancreatic islet inwardly rectifying potassium channel: cDNA cloning, determination of the genomic structure and genetic variations in Japanese NIDDM patients

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Summary

Ligand gated potassium channels, such as the ATP-regulated potassium channel, play crucial roles in coupling of stimuli to insulin secretion in pancreatic beta cells. Mutations in the genes might lead to the insulin secretory defects observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). We isolated a cDNA encoding a putative subunit of a ligand gated potassium channel from a human islet cDNA library. The channel, which we designated hiGIRK2, appeared to be an alternative spliced variant and a human homologue of recently reported mbGIRK2, KATP-2/BIR1. Transcripts were detected in human brain and pancreas, but not in other tissues including cardiac muscle. The sizes of transcripts in the pancreas differed from those in the brain, suggesting tissue-specific alternative splicing and possible isoforms. We then isolated human genomic clones, determined the complete genomic structure and localized the gene to chromosome 21 (21q22). The gene was comprised of four exons and the protein was encoded by three exons. The entire coding region of the hiGIRK2 gene was scanned by polymerase chain reaction-single strand conformation polymorphism analysis in 80 Japanese NIDDM patients. We found five nucleotide substitutions; three were silent mutations of the third base of codons, one in the first intron, 9 bases upstream of exon 2, and one in the 3′-untranslated region. We conclude that mutations in the gene encoding MGIRK2, a (subunit of) ligand gated potassium channel, is not a major determinant of the susceptibility to NIDDM in Japanese.

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Abbreviations

NIDDM:

Non-insulin-dependent diabetes mellitus

cDNA:

complementary DNA

PCR:

polymerase chain reaction

SSCP:

single strand conformation polymorphism

K-DR:

delayed rectifying (voltage-dependent) potassium channel

K-ATP:

ATP (adenine nucleotide) regulated potassium channel

K-Ca:

Ca2+ activated potassium channel

K-I:

inhibitor activated potassium channel

ORF:

open reading frame

SUR:

sulfonylurea receptor

ORCC:

outward rectifying chloride channel

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Tanizawa, Y., Matsubara, A., Ueda, K. et al. A human pancreatic islet inwardly rectifying potassium channel: cDNA cloning, determination of the genomic structure and genetic variations in Japanese NIDDM patients. Diabetologia 39, 447–452 (1996). https://doi.org/10.1007/BF00400676

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  • DOI: https://doi.org/10.1007/BF00400676

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