Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM

Diabetes. 1995 May;44(5):592-6. doi: 10.2337/diab.44.5.592.

Abstract

The metabolism of glucose in insulin-secreting cells leads to closure of ATP-sensitive K+ channels (KATP), an event that initiates the insulin secretory process. Defects in insulin secretion are a common feature of non-insulin-dependent diabetes mellitus (NIDDM), and the beta-cell KATP that couples metabolism and membrane potential is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder. We screened a hamster insulinoma cDNA library by low-stringency hybridization with a probe coding for the G-protein-coupled inwardly rectifying K+ channel GIRK1/KGA and isolated clones encoding a protein, KATP-2, whose sequence is 90% similar to that of the recently described KATP-1, an ATP-sensitive K+ channel expressed in heart and other tissues. RNA blotting showed that KATP mRNA was present in insulin-secreting cells and brain but not in heart. To assess the contribution of KATP-2 to the development of NIDDM, the human KATP-2 gene (symbol KCNJ7) was isolated and mapped to chromosome band 21q22.1 by fluorescence in situ hybridization. A simple tandem repeat DNA polymorphism, D21S1255, was identified in the region of the KATP-2 gene, and linkage studies between this marker and NIDDM were carried out in a group of Mexican-American sib pairs with NIDDM. There was no evidence for linkage between D21S1255 and NIDDM, indicating that KATP-2 is not a major susceptibility gene in this population.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Artificial, Yeast
  • Chromosomes, Human, Pair 21*
  • Cricetinae
  • DNA Primers / genetics
  • DNA, Complementary / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Genetic Linkage
  • Humans
  • In Situ Hybridization, Fluorescence
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Molecular Sequence Data
  • Potassium Channels / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • DNA, Complementary
  • Insulin
  • Potassium Channels
  • RNA, Messenger
  • Adenosine Triphosphate

Associated data

  • GENBANK/U21937