Sodium channel beta1 regulatory subunit deficiency reduces pancreatic islet glucose-stimulated insulin and glucagon secretion.
Glucose-stimulated insulin and glucagon release regulates glucose homeostasis by an excitation-secretion coupling pathway beginning with ATP-sensitive K(+) channel closure, membrane depolarization, and entry of calcium ions to stimulate exocytosis. The contribution of voltage-gated sodium channels to this release pathway is still being elucidated. We demonstrate that loss of Scn1b, a major regulatory subunit expressed with Na(v)1.7 protein in mouse pancreatic islets, reduces glucose-stimulated insulin and glucagon secretion in vitro and in vivo, resulting in severe fed and fasting hypoglycemia. This genetic mouse model is the first to demonstrate that sodium channelopathy impairs the physiological excitation-release coupling pathway for pancreatic insulin and glucagon release.
Ernst
Sara J
SJ
Departments of Molecular and Human Genetics, Developmental Neurogenetics Laboratory, Baylor College of Medicine, Houston, Texas 77030, USA.
Aguilar-Bryan
Lydia
L
Noebels
Jeffrey L
JL
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007003:Hypoglycemia / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
D007328:Insulin; C524974:Scn1b protein, mouse; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D005934:Glucagon; D005947:Glucose