Functional effects of transgenic expression of cholera toxin in pancreatic beta-cells

Lise Wogensen, Ma Yan-Hui, Gerold M. Grodsky, R. Paul Robertson, Frank Burton, J. Gregor Sutcliffe, Nora Sarvetnick

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Investigation of intracellular pathways of stimulus-secretion signaling in vivo is possible by transgenic expression of agents known to influence specific biochemical interactions in the cells. The objective of the present study was to establish an experimental model for analyzing signal transduction mechanisms in pancreatic beta-cells in vivo, by expressing the cholera toxin A1 subunit under control of the insulin promoter, intending a constant activation of the Gs-protein, and thereby constant generation of cAMP. Surprisingly, the transgenic mice demonstrated mild hyperglycemia and hypoinsulinemia in vivo, and diminished glucose-induced insulin release from the in vitro perfused pancreas, whereas the pancreatic insulin content was normal. These observations suggest a deficiency in either the insulin release mechanisms or glucose recognition. Although the translated cholera toxin A1 subunit was biologically active, there was no increase in the islet content of cAMP. We conclude that the observed phenotype in the cholera toxin transgenic mice may be caused by a deleterious effect of the transgene itself on beta-cell function, or that counter regulatory mechanisms may compensate for the transgene-induced changes in intracellular enzymatic pathways.

Original languageEnglish (US)
Pages (from-to)33-42
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume98
Issue number1
DOIs
StatePublished - Dec 1993

Fingerprint

Cholera Toxin
Insulin-Secreting Cells
Insulin
Transgenes
Transgenic Mice
Glucose
Signal transduction
Secretory Pathway
Cell Communication
Hyperglycemia
Pancreas
Signal Transduction
Theoretical Models
Chemical activation
Phenotype
Proteins

Keywords

  • /gb-Cell
  • Cholera toxin
  • Cyclic AMP
  • Insulin release
  • Transgene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Functional effects of transgenic expression of cholera toxin in pancreatic beta-cells. / Wogensen, Lise; Yan-Hui, Ma; Grodsky, Gerold M.; Robertson, R. Paul; Burton, Frank; Sutcliffe, J. Gregor; Sarvetnick, Nora.

In: Molecular and Cellular Endocrinology, Vol. 98, No. 1, 12.1993, p. 33-42.

Research output: Contribution to journalArticle

Wogensen, Lise ; Yan-Hui, Ma ; Grodsky, Gerold M. ; Robertson, R. Paul ; Burton, Frank ; Sutcliffe, J. Gregor ; Sarvetnick, Nora. / Functional effects of transgenic expression of cholera toxin in pancreatic beta-cells. In: Molecular and Cellular Endocrinology. 1993 ; Vol. 98, No. 1. pp. 33-42.
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