Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y

Wendy M. Macfarlane, Rachel E. O'Brien, Philippa D. Barnes, Ruth M. Shepherd, Karen E. Cosgrove, Keith J. Lindley, Albert Aynsley-Green, Roger F L James, Kevin Docherty, Mark J. Dunne

    Research output: Contribution to journalArticlepeer-review


    NES2Y is a proliferating human insulin-secreting cell line that we have derived from a patient with persistent hyperinsulinemic hypoglycemia of infancy. This disease is characterized by unregulated insulin release despite profound hypoglycemia. NES2Y cells, like β-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (K(ATP)) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. Here, we report that the NES2Y β-cells that are transfected with the genes encoding the components of K(ATP) channels in β-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational K(ATP) channels and show normal intracellular Ca2+ and secretory responses to glucose. However, these cells, designated NESK β-cells, have impaired insulin gene transcription responses to glucose. NES2Y β-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional K(ATP) channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent β-cell agonists. These findings document that in NES2Y β-cells, coexpression of both subunits is critically required for fully operational K(ATP) channels and K(ATP) channel-dependent signaling events. This article further characterizes the properties of the novel human β-cell line, NES2Y, and documents the usefulness of these cells in diabetes- related research.
    Original languageEnglish
    Pages (from-to)953-960
    Number of pages7
    Issue number6
    Publication statusPublished - Jun 2000


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