Single pancreatic B cells are purified by autofluorescence- activated cell sorting, and their secretory activity is measured after overnight culture. Compared to intact islets, the isolated cells release 2-fold more insulin under basal conditions and 5-fold less during nutrient stimulation. Their secretory activity can be induced by glucose, leucine, or arginine, but only 0.3–1.7% of their hormone content is liberated at 20 mm nutrient concentrations. This poor nutrient-induced insulin release from purified B cells is attributed to their low cAMP levels and is markedly increased after addition of (Bu)²cAMP, of glucagon, or of pancreatic A cells.

These results strongly support the concept that the potent in vivo insulin-releasing action of glucose and leucine is not only dependent on their fuel capacity in pancreatic B cells but also on the concurrent cAMP levels in these cells. In isolated islets, endogenously released glucagon apparently determines the cAMP production in B cells and thus participates in the nutrient- induced secretory process. Somatostatin and epinephrine were shown to exert their suppressive effects via the glucagondependent messenger system.

It is concluded that nutrients and hormones interact with two different messenger systems which amplify each others’ stimulatory effect upon insulin release. cAMP might represent the hormone-induced messenger which sets the B cell’s sensitivity and secretory capacity for nutrient stimuli such as glucose.

The higher insulin secretory response observed after reaggregation of single B cells could not be attributed to an altered activity in the nutrient or hormonal regulatory units, raising the possibility that the aggregated state of the cells is rather responsible for a better organization or cooperation of the secretory effector unit. (Endocrinology117: 824–833, 1985)