Glucose exerts opposite effects on muscarinic receptor binding to A and B cells of the endocrine pancreas.

Ambient glucose stimulates insulin but inhibits glucagon secretion. We investigated whether mirror-image regulation pertains also to glucose effects on muscarinic receptor binding to B and A cells. We compared binding of [3H]methylscopolamine to islets from normal guinea pigs and to A-cell rich islets from streptozotocin-treated animals. Binding was assessed in intact islets at 37 C after previous culture for 72 h in 3.3, 5.5, or 11 mM glucose. For both types of islets, specific binding was observed after 1 min and reached a plateau after 10 min of incubation. Half-maximal displacement of 2.8 X 10(-9) M [3H] methylscopolamine occurred with 10(-9) - 10(-8) M unlabeled methylscopolamine. In normal islets, specific binding was significantly higher after culture in 11 mM than after 3.3 or 5.5 mM glucose. Conversely, in A-cell rich islets, binding was significantly higher at 3.3 or 5.5 than at 11 mM glucose. Glucagon release induced by acetylcholine (10(-5) M) was half-maximally suppressed by methylscopolamine at a concentration of 10(-9) - 10(-8) M. Acetylcholine-stimulated glucagon release was higher from A-cell rich islets when cultured at 3.3 mM than when cultured at 11 mM glucose. It is concluded: 1) that both A and B cells appear to contain muscarinic receptors, 2) that long term glucose environment exerts opposite effects on binding of methylscopolamine to A and B cells, and 3) that inhibition of binding to A cells is correlated with reduction of acetylcholine-induced glucagon release.