Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(v)2.3 (alpha 1E) subunit of voltage-gated Ca(2+) channels.
Multiple types of voltage-activated Ca(2+) channels (T, L, N, P, Q, R type) coordinate Ca(2+)-dependent processes in neurons and neuroendocrine cells. Expressional and functional data have suggested a role for Ca(v)2.3 Ca(2+) channels in endocrine processes. To verify its role in vivo, Ca(v)2.3(-/-) mutant mice were generated, thus deficient in alpha 1E/R-type Ca(2+) channel. Intraperitoneal injection of D-glucose showed that glucose tolerance was markedly reduced, and insulin release into plasma was impaired in Ca(v)2.3-deficient mice. In isolated islets of Langerhans from these animals, no glucose-induced insulin release was detected. Further, in stressed Ca(v)2.3-deficient mice, the rate of glucose release into the blood was only 29% of that observed for wild-type animals. Thus, the deletion of Ca(v)2.3 causes deficits not only in insulin release but also in stress-induced hyperglycemia. The complex phenotype of Ca(v)2.3-deficient mice has dual components related to endocrine and neurological defects. The present findings provide direct evidence of a functional role for the Ca(v)2.3 subunit in hormone secretion and glucose homeostasis.
Pereverzev
Alexey
A
Institute of Neurophysiology, University of Cologne, D-50931 Köln, Germany.
Mikhna
Marina
M
Vajna
Rolf
R
Gissel
Cornelia
C
Henry
Margit
M
Weiergräber
Marco
M
Hescheler
Jürgen
J
Smyth
Neil
N
Schneider
Toni
T
D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D005260:Female; D005947:Glucose / Q000502:physiology*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006943:Hyperglycemia / Q000209:etiology*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013312:Stress, Physiological / Q000150:complications*
C498916:Cacna1e protein, mouse; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D007328:Insulin; D005947:Glucose