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Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(V)2.3 (alpha 1E) subunit of voltage-gated Ca2+ channels

Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(V)2.3 (alpha 1E) subunit of voltage-gated Ca2+ channels
Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(V)2.3 (alpha 1E) subunit of voltage-gated Ca2+ channels
Multiple types of voltage-activated Ca2+ channels (T, L, N, P, Q, R type) coordinate Ca2+-dependent processes in neurons and neuroendocrine cells. Expressional and functional data have suggested a role for Cav2.3 Ca2+ channels in endocrine processes. To verify its role in vivo, Cav2.3(-/-) mutant mice were generated, thus deficient in {alpha}1E/R-type Ca2+ channel. Intraperitoneal injection of D-glucose showed that glucose tolerance was markedly reduced, and insulin release into plasma was impaired in Cav2.3-deficient mice. In isolated islets of Langerhans from these animals, no glucose-induced insulin release was detected. Further, in stressed Cav2.3-deficient mice, the rate of glucose release into the blood was only 29% of that observed for wild-type animals. Thus, the deletion of Cav2.3 causes deficits not only in insulin release but also in stress-induced hyperglycemia. The complex phenotype of Cav2.3-deficient mice has dual components related to endocrine and neurological defects. The present findings provide direct evidence of a functional role for the Cav2.3 subunit in hormone secretion and glucose homeostasis.
0888-8809
884-895
Pereverzev, A.
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Mikhna, M.
bcefa436-f5b6-4235-97fc-d23781a170cd
Vajna, R.
75de7208-2898-44e6-97be-88f36cf4a302
Gissel, C.
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Henry, M.
f20af19b-884c-45b7-a263-276113bbb327
Weiergraber, M.
e42756d4-2de8-40f1-98de-87f2fbf54ba6
Hescheler, J.
b974a26f-9019-43f5-bf03-776f4886224c
Smyth, N.
0eba2a40-3b43-4d40-bb64-621bd7e9d505
Schneider, T.
ddc7c577-d358-4713-bb39-7c3db06b78ab
Pereverzev, A.
4ad3b4f9-81f3-4560-97d8-1c28b1a0f263
Mikhna, M.
bcefa436-f5b6-4235-97fc-d23781a170cd
Vajna, R.
75de7208-2898-44e6-97be-88f36cf4a302
Gissel, C.
f6719741-318f-4185-9369-fde091b0602a
Henry, M.
f20af19b-884c-45b7-a263-276113bbb327
Weiergraber, M.
e42756d4-2de8-40f1-98de-87f2fbf54ba6
Hescheler, J.
b974a26f-9019-43f5-bf03-776f4886224c
Smyth, N.
0eba2a40-3b43-4d40-bb64-621bd7e9d505
Schneider, T.
ddc7c577-d358-4713-bb39-7c3db06b78ab

Pereverzev, A., Mikhna, M., Vajna, R., Gissel, C., Henry, M., Weiergraber, M., Hescheler, J., Smyth, N. and Schneider, T. (2002) Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(V)2.3 (alpha 1E) subunit of voltage-gated Ca2+ channels. Molecular endocrinology, 16 (4), 884-895.

Record type: Article

Abstract

Multiple types of voltage-activated Ca2+ channels (T, L, N, P, Q, R type) coordinate Ca2+-dependent processes in neurons and neuroendocrine cells. Expressional and functional data have suggested a role for Cav2.3 Ca2+ channels in endocrine processes. To verify its role in vivo, Cav2.3(-/-) mutant mice were generated, thus deficient in {alpha}1E/R-type Ca2+ channel. Intraperitoneal injection of D-glucose showed that glucose tolerance was markedly reduced, and insulin release into plasma was impaired in Cav2.3-deficient mice. In isolated islets of Langerhans from these animals, no glucose-induced insulin release was detected. Further, in stressed Cav2.3-deficient mice, the rate of glucose release into the blood was only 29% of that observed for wild-type animals. Thus, the deletion of Cav2.3 causes deficits not only in insulin release but also in stress-induced hyperglycemia. The complex phenotype of Cav2.3-deficient mice has dual components related to endocrine and neurological defects. The present findings provide direct evidence of a functional role for the Cav2.3 subunit in hormone secretion and glucose homeostasis.

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Published date: 1 April 2002

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Local EPrints ID: 56119
URI: http://eprints.soton.ac.uk/id/eprint/56119
ISSN: 0888-8809
PURE UUID: 780f96da-0f65-4c53-a11e-f809f0bafabb

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Date deposited: 08 Aug 2008
Last modified: 08 Jan 2022 04:02

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Contributors

Author: A. Pereverzev
Author: M. Mikhna
Author: R. Vajna
Author: C. Gissel
Author: M. Henry
Author: M. Weiergraber
Author: J. Hescheler
Author: N. Smyth
Author: T. Schneider

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