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

Mol Endocrinol. 2002 Apr;16(4):884-95. doi: 10.1210/mend.16.4.0801.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / physiology*
  • Calcium Channels, R-Type
  • Cation Transport Proteins*
  • Female
  • Glucose / physiology*
  • Glucose Tolerance Test
  • Homeostasis
  • Hyperglycemia / etiology*
  • Injections, Intraperitoneal
  • Insulin / metabolism*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Stress, Physiological / complications*


  • Cacna1e protein, mouse
  • Calcium Channels
  • Calcium Channels, R-Type
  • Cation Transport Proteins
  • Insulin
  • Glucose