Disturbances in Glucose-Tolerance, Insulin-Release, and Stress-Induced Hyperglycemia upon Disruption of the Cav2.3 (α1E) Subunit of Voltage-Gated Ca2+ …

A Pereverzev, M Mikhna, R Vajna… - Molecular …, 2002 - academic.oup.com
A Pereverzev, M Mikhna, R Vajna, C Gissel, M Henry, M Weiergräber, J Hescheler…
Molecular Endocrinology, 2002academic.oup.com
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 α1E/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 …
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 α1E/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.
Oxford University Press