Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion.
Sur1 knockout mouse beta-cells lack K(ATP) channels and show spontaneous Ca(2+) action potentials equivalent to those seen in patients with persistent hyperinsulinemic hypoglycemia of infancy, but the mice are normoglycemic unless stressed. Sur1(-/-) islets lack first phase insulin secretion and exhibit an attenuated glucose-stimulated second phase secretion. Loss of the first phase leads to mild glucose intolerance, whereas reduced insulin output is consistent with observed neonatal hyperglycemia. Loss of K(ATP) channels impairs the rate of return to a basal secretory level after a fall in glucose concentration. This leads to increased hypoglycemia upon fasting and contributes to a very early, transient neonatal hypoglycemia. Whereas persistent hyperinsulinemic hypoglycemia of infancy underscores the importance of the K(ATP)-dependent ionic pathway in control of insulin release, the Sur1(-/-) animals provide a novel model for study of K(ATP)-independent pathways that regulate insulin secretion.
Seghers
V
V
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nakazaki
M
M
DeMayo
F
F
Aguilar-Bryan
L
L
Bryan
J
J
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D007003:Hypoglycemia; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000378:metabolism; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors