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Previous in vivo findings indicated that α-adrenergic blocking agents enhanced tolbutamide-induced insulin secretion, whereas β-blockade attenuated it. In the present study, the interaction of tolbutamide and glyburide with the rat islet adrenergic receptors is examined directly by determining the effectiveness of these drugs to displace the specific α- and β-adrenergic radioligands, [3H]-clonidine and [3H]-dihydroalprenolol (DHA). It was found that both tolbutamide and glyburide had affinity constants for the adrenergic receptors that were similar to those for the natural receptor ligands and powerful antagonists. Tolbutamide displaced both α- and β-radioligands but had a higher affinity at the β-receptor. Glyburide also displaced radioligands from both types of receptors but had a higher affinity for the α-receptor. This study suggests that these two sulfonylurea hypoglycemic agents may affect insulin secretion by different mechanisms.

Tolbutamide and Glyburide Differ in Effectiveness to Displace α-and β-Adrenergic Radioligands in Pancreatic Islet Cells and Membranes