Decreased insulin content and secretion in RIN 1046-38 cells overexpressing alpha 2-adrenergic receptors.
Several Gi-protein-coupled receptors normally expressed in islet beta-cells inhibit insulin secretion on binding of their respective agonists. To study the effect of supraphysiologic expression of such a receptor in insulin-secreting beta-cells, we stably transfected cDNA encoding the mouse alpha 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected, each overexpressing the alpha 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 (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 beta-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.
Rodriguez-Pena
M S
MS
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Collins
R
R
Woodard
C
C
Spiegel
A M
AM
D000818:Animals; D000911:Antibodies, Monoclonal; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D037342:Pertussis Toxin; D011189:Potassium Chloride / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007004:Hypoglycemic Agents; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D005749:Gastric Inhibitory Polypeptide; D011189:Potassium Chloride; D002217:Carbachol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005947:Glucose; D005905:Glyburide