Effects of an enkephalin analogue (DAMME) on insulin release from cultured rat islets of Langerhans.

Rat islets of Langerhans were maintained for 2 days in tissue culture. Following the culture period, the insulin secretory responses of the islets on incubation in bicarbonate medium were measured. The enkephalin analogue D-ala2, MePhe4, Met(0)-ol (DAMME), 8.3 X 10(-8) mol/l, augmented insulin release stimulated by glucose (5 or 7 mmol/l) by 76% and 47% respectively; increased insulin release stimulated by alpha-ketoisocaproate (7.5 mmol/l) by 23%; and enhanced insulin release in the presence of glibenclamide (10 microgram/ml) plus glucose (3.3 mmol/l) by 38%. Insulin release in the presence of glucose at 2 or 12 mmol/l was not affected by DAMME (8.3 X 10(-8) mol/l). The potentiatory effect of DAMME on insulin release in the presence of glucose (5 mmol/l) was blocked by naloxone (11 mumol/l): naloxone alone did not affect glucose-stimulated insulin release. A high concentration (3.3 X 10(-6) mol/l) of DAMME did not modify glucose-stimulated insulin release. Inhibition of glucose-stimulated insulin release by trifluoperazine, an inhibitor of calmodulin, was not overcome by DAMME. Insulin secretory responses were not enhanced by exposure of the islets to DAMME (8.3 X 10(-8) mol/l) during the culture period. It is concluded that insulin release from isolated islets is capable of being influenced by an opioid peptide.