The control of insulin secretion in the cell involves both stimulatory and inhibitory pathways. Gi protein-coupled receptors such as those for galanin, somatostatin or a2 adrenergic agonists, have been found to be normally expressed in islets/ cells where they play an important role in the physiologic inhibition of insulin secretion (1). To study the effect of supraphysiologic expression of an inhibitory receptor in insulin-secreting/ cells we stably transfected expression vectors pREP4 and pCDNA3 containing an epitope tagged a 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected each overexpressing the a 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin treatment of cells was able to partially reverse the reduced insulin secretory response. Our results suggest that overexpression of a Giprotein-coupled receptor in islets/ cells can impair insulin secretion. Abnormalities in expression or function, e.g. constitutively activating mutations of such receptors could contribute to impaired insulin secretion in type II diabetes. (1). McDdermott, A.M. and Sharp, G.W, 1993. Inhibition of insulin secretion: a fall-safe system. Cell. Signal. 5:. 229.
|Original language||English (US)|
|Publication status||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology