title: Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells.
abstract: ATP-sensitive potassium channels (KATPchannels) are critical nutrient sensors in many mammalian tissues. In the pancreas, KATPchannels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism-secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear. In this paper, we demonstrate that zebrafish islet β-cells express functional KATPchannels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts. We further show that pharmacological activation of native zebrafish KATPusing diazoxide, a specific KATPchannel opener, is sufficient to disturb glucose tolerance in adult zebrafish. That β-cell KATPchannel expression and function are conserved between zebrafish and mammals illustrates the evolutionary conservation of islet metabolic sensing from fish to humans, and lends relevance to the use of zebrafish to model islet glucose sensing and diseases of membrane excitability such as neonatal diabetes.
authors.affiliation: Department of Cell Biology and Physiology, Washington University in St Louis, St Louis, MO, USA; Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St Louis, St Louis, MO, USA; Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Emfinger
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St Louis, St Louis, MO, USA; Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Alecia
authors.initials: A
authors.lastname: Welscher
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St Louis, St Louis, MO, USA; Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Cell Biology and Physiology, Washington University in St Louis, St Louis, MO, USA; Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Yixi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine , Washington University in St Louis , St Louis, MO , USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Conway
authors.affiliation: Division of Endocrinology, Metabolism, and Nutrition and DMPI , Duke University Medical Center , Durham, NC , USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Moss
authors.affiliation: Division of Endocrinology, Metabolism, and Nutrition and DMPI , Duke University Medical Center , Durham, NC , USA.
authors.forename: Larry G
authors.initials: LG
authors.lastname: Moss
authors.affiliation: Department of Cell Biology and Physiology, Washington University in St Louis, St Louis, MO, USA; Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St Louis, St Louis, MO, USA; Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Remedi
authors.affiliation: Department of Cell Biology and Physiology, Washington University in St Louis, St Louis, MO, USA; Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Colin G
authors.identifier: 0000-0002-4929-2134
authors.initials: CG
authors.lastname: Nichols
keywords: KATP; ion channels; metabolism; pancreas; zebrafish