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.
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.
Pereverzev
Alexey
A
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.
Salehi
Albert
A
Mikhna
Marina
M
Renström
Erik
E
Hescheler
Jürgen
J
Weiergräber
Marco
M
Smyth
Neil
N
Schneider
Toni
T
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
D001786:Blood Glucose; D015220:Calcium Channels; D027682:Cation Transport Proteins; D007328:Insulin; D002217:Carbachol; D005934:Glucagon; D005947:Glucose