In vitro kinetics of insulin release by microencapsulated rat islets: effect of the size of the microcapsules.

Microencapsulation has been proposed to protect islets of Langerhans against immune rejection in xenogenic transplantation. However, to achieve glucose homeostasis in human diabetic patients, insulin release by microencapsulated islets must increase in response to a glucose load. We microencapsulated isolated rat islets using the alginate-polylysine procedure. Capsule size was found to range from 300 to 800 micron, and microencapsulated islets were separated according to their size. Groups of 10 microencapsulated islets, either small (350 micron) or large (650 micron) were placed in plastic microwells, in minimal Eagle's culture medium containing either 5.5 mol/l glucose (basal) or 16.5 mol/l glucose and 5.5 mol/l theophylline (stimulatory medium). The increase in insulin concentration in the surrounding medium was then serially determined over 30 min: (1) With the small capsules, insulin concentration rose from 199 +/- 20 to 297 +/- 58 microU/ml in basal medium, and from 236 +/- 23 to 510 +/- 121 microU/ml in stimulatory medium (n = 10 preparations), the difference between the data obtained with the basal or the stimulatory medium being significant (p less than 0.01) from the 5th min onwards. (2) With large capsules, insulin concentration increased from 182 +/- 9 to 266 +/- 44 microU/ml, and from 216 +/- 19 to 297 +/- 34 microU/ml in basal and stimulatory medium, respectively, with no apparent significant difference. The magnitude of insulin secretion in response to glucose by unencapsulated islets was, under similar conditions, seven-fold greater. We conclude therefore that the size of the microcapsules is an essential parameter which has to be considered for the optimisation of the microencapsulation procedure.