Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Epstein PN,Overbeek PA,Means ARdoi
10.1016/0092-8674(89)90505-9subject
Has Abstractpub_date
1989-09-22 00:00:00pages
1067-73issue
6eissn
0092-8674issn
1097-4172pii
0092-8674(89)90505-9journal_volume
58pub_type
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