The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor

mal subjects after rapid intravenous injection of glucose (5 g) or isoproterenol (2 Atg) were of similar magnitude and timing (glucose: 431±349%; mean A3-5 ' insulin (IRI) ±SD, per cent basal and isoproterenol: 359+ 216%; mean A2-4 ' IRI-+-SD, per cent basal). To eluci-date the relationship of glucose-induced insulin secretion to pancreatic beta adrenergic receptors and the implica-tions of this relationship with regards to abnormal in-sulin secretion in diabetes mellitus, two questions were studied. (a) To determine whether glucose-induced in-sulin secretion is dependent upon beta adrenergic ac-tivity, the effect of beta adrenergic blockade with intra-venous propranolol (0.08 mg/min) upon acute insulin responses to isoproterenol and glucose were compared in normal subjects. (b) To determine whether acute insulin responses to beta adrenergic stimulation were intact in dia-betes mellitus, the effect of isoproterenol upon serum insu-lin levels was studied in diabetic subjects. Beta adrenergic blockade in the normal subjects obliterated acute insulin responses to isoproterenol (before: 361±270%, during:- 31±15%; n = 6, P < 0.001) but did not significantly affect responses to glucose (before: 311±270%; during: 284±206%; n = 5). The mean acute insulin response after isoproterenol in the diabetic group was significantly elevated over basal levels ( 152±74%; n = 10, P < 0.001) but the response after glucose was not (- 11+ ± 11%). These data suggest that insulin responses to glucose in normal subjects are mediated by specific pancreatic glucose receptors which are independent from beta adrenergic receptors and that abnormal glucose-induce