title: The ablation of the Ca(v)2.3/E-type voltage-gated Ca2+ channel causes a mild phenotype despite an altered glucose induced glucagon response in isolated islets of Langerhans.
abstract: Glucagon release upon hypoglycemia is an important homeostatic mechanism utilized by vertebrates to restore blood glucose to normal. Glucagon secretion itself is triggered by Ca2+ influx through voltage-gated ion channels, and the gene inactivation of R-type Ca2+ channels, with Ca(v)2.3 as the ion conducting subunit, has been shown to disturb glucose homeostasis. To understand how glucagon release may be affected in Ca(v)2.3-deficient mice, carbachol, insulin and glucose induced glucagon response was investigated. While the rise of insulin and glucose induced by carbachol is normal, mutant mice show an impaired glucagon-response. Further, the effect of insulin injection on glucagon levels was altered by the loss of the Ca(v)2.3 subunit. Ca(v)2.3-deficient mice are characterized by an impaired glucose suppression of glucagon release. This was most obvious at the level of isolated islets suggesting that Ca(v)2.3 containing R-type voltage-gated Ca2+ channels are involved in the glucose-mediated signalling to glucagon release in mice.
authors.affiliation: Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, D-50931 Köln, Germany; Center of Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 39, D-50931 Köln, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Pereverzev
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
authors.forename: Marina
authors.initials: M
authors.lastname: Mikhna
authors.forename: Erik
authors.initials: E
authors.lastname: Renström
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Marco
authors.initials: M
authors.lastname: Weiergräber
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
authors.forename: Toni
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D015220:Calcium Channels; D027682:Cation Transport Proteins; D007328:Insulin; D002217:Carbachol; D005934:Glucagon; D005947:Glucose