Abstract
Several Gi-protein-coupled receptors normally expressed in islet β-cells inhibit insulin secretion on binding of their respective agonists. To study the effect of supraphysiologic expression of such a receptor in insulin-secreting β-cells, we stably transfected cDNA encoding the mouse α2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected, each overexpressing the α2a-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 (PTX) treatment of cells was able to reverse partially the reduced insulin secretory response. Our results suggest that overexpression of a Gi-protein-coupled receptor in β-cells causes tonic inhibition of both insulin synthesis and secretion. Abnormalities in expression or function of such receptors could be a contributory factor in the impaired insulin secretion present in type II diabetes.
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Rodriguez-Pena, M.S., Collins, R., Woodard, C. et al. Decreased insulin content and secretion in RIN 1046-38 cells overexpressing α2-Adrenergic receptorsreceptors. Endocr 7, 255–260 (1997). https://doi.org/10.1007/BF02778148
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DOI: https://doi.org/10.1007/BF02778148