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Calmodulin-induced early-onset diabetes in transgenic mice.

Publication ,  Journal Article
Epstein, PN; Overbeek, PA; Means, AR
Published in: Cell
September 22, 1989

Calmodulin is implicated as the primary transducer of the calcium signal in pancreatic beta cells, where it is present at very high concentrations. We have produced three lines of transgenic mice carrying a calmodulin minigene regulated by the rat insulin II promoter. Immunohistochemistry and hybridization analyses indicated a 5-fold increase in the content of calmodulin and its mRNA in beta cells. Transgenic mice developed severe diabetes within hours of birth. The diabetes was progressive and characterized by elevated blood glucose and glucagon that coincided with reduced serum and pancreatic insulin. The disease appears to have both secretory and cell destruction components. beta Cell pathology was evident in the diabetic neonate but not in the fetus, suggesting that the early onset of diabetes exacerbated possible toxic effects of excess calmodulin. These animals provide a new diabetes model to evaluate how abnormal calcium homeostasis alters the carefully programmed secretory activity and development of the beta cell.

Duke Scholars

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

September 22, 1989

Volume

58

Issue

6

Start / End Page

1067 / 1073

Location

United States

Related Subject Headings

  • Signal Transduction
  • Reference Values
  • Mice, Transgenic
  • Mice
  • Islets of Langerhans
  • Insulin
  • Glucagon
  • Genetic Vectors
  • Female
  • Diabetes Mellitus, Type 2
 

Citation

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Epstein, P. N., Overbeek, P. A., & Means, A. R. (1989). Calmodulin-induced early-onset diabetes in transgenic mice. Cell, 58(6), 1067–1073. https://doi.org/10.1016/0092-8674(89)90505-9
Epstein, P. N., P. A. Overbeek, and A. R. Means. “Calmodulin-induced early-onset diabetes in transgenic mice.Cell 58, no. 6 (September 22, 1989): 1067–73. https://doi.org/10.1016/0092-8674(89)90505-9.
Epstein PN, Overbeek PA, Means AR. Calmodulin-induced early-onset diabetes in transgenic mice. Cell. 1989 Sep 22;58(6):1067–73.
Epstein, P. N., et al. “Calmodulin-induced early-onset diabetes in transgenic mice.Cell, vol. 58, no. 6, Sept. 1989, pp. 1067–73. Pubmed, doi:10.1016/0092-8674(89)90505-9.
Epstein PN, Overbeek PA, Means AR. Calmodulin-induced early-onset diabetes in transgenic mice. Cell. 1989 Sep 22;58(6):1067–1073.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

September 22, 1989

Volume

58

Issue

6

Start / End Page

1067 / 1073

Location

United States

Related Subject Headings

  • Signal Transduction
  • Reference Values
  • Mice, Transgenic
  • Mice
  • Islets of Langerhans
  • Insulin
  • Glucagon
  • Genetic Vectors
  • Female
  • Diabetes Mellitus, Type 2