Absence of effect of heparin on insulin secretion.

Bioartificial pancreatic devices containing isolated islets of Langerhans have been designed, in which the blood of the recipient circulates in contact with an artificial membrane, protecting the islets against immune rejection. This system assumes that heparin, required to prevent blood clotting, does not alter insulin secretion. However, heparin has been reported to inhibit in vitro insulin secretion by rat islets and to suppress in vivo insulin secretion in dogs. Therefore, the following evaluation was made on the effect of different heparin preparations on insulin secretion. (a) Isolated rat islets of Langerhans were perfused or incubated in the absence or presence of 20 micrograms/ml heparin; insulin secretion in response to a stimulation by glucose 20 mM was not altered by the presence of heparin. (b) Insulin secretion by an insulin-secreting cell line (RINm5F) in response to leucine and theophylline was not suppressed by heparin up to 100 micrograms/ml concentration. However, an inhibitory effect was observed at 200 micrograms/ml, which is 100 times higher than the heparin concentration commonly used for therapeutic use. (c) Neither in normal rats nor in dogs did heparin alter portal plasma insulin levels and the increase in plasma insulin following an intravenous injection of glucose. In conclusion, these data do not confirm the formerly observed inhibitory effect of heparin, which can therefore be used for the in vivo evaluation of a bioartificial pancreas.