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 β-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.
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
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Meei-Ling Tsaur, Stephan Menzel, Fang P Lai, Rafael Espinosa, Patrick Concannon, Richard S Spielman, Craig L Hanis, Nancy J Cox, Michelle M Le Beau, Michael S German, Lily Y Jan, Graeme I Bell, Markus Stoffel; 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 1 May 1995; 44 (5): 592–596. https://doi.org/10.2337/diab.44.5.592
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