Macroaggregated albumin potentiates the hypoglycemic effect of microencapsulated islets in the fed state of streptozotocin-induced diabetic mice.

Prolonged postprandial hyperglycaemia was noted in streptozotocin-induced diabetic mice which had been treated intraperitoneally with 2000-3000 alginate-poly-L-lysine-alginate (A-P-A) microencapsulated rat islets. We hypothesized that the persistent postprandial hyperglycaemia was due to shortage of intracapsular calcium ion. In order to study the effect of encapsulated macroaggregated albumin (MAA) on the function of microencapsulated islets, we coencapsulated MAA and islets in A-P-A microcapsules which we implanted intraperitoneally into streptozotocin-induced diabetic mice. From binding study and Scatchard analysis, we found that MAA-containing A-P-A microcapsules had a lower calcium binding affinity 5.24 +/- 1.20 mM versus 2.35 +/- 0.86 mM, n = 12, p < 0.01) and a higher calcium binding capacity (14.34 +/- 1.22 micrograms/mg versus 7.24 +/- 0.82 micrograms/mg, n = 12, p < 0.01) than empty A-P-A microcapsules. After intraperitoneal transplantation of 2000-3000 microcapsules containing islets and encapsulated MAA, the basal and postprandial blood glucose levels of the treated diabetic mice were not significantly different from that of normal mice. The improvement of persistent postprandial hyperglycaemia in these treated diabetic mice was not due to the difference of food intake in amount. In conclusion, A-P-A microcapsules containing islets and encapsulated MAA functioned better than microcapsules containing islets alone in treating streptozotocin-induced diabetic mice. The former preparation restored both fasting and postprandial hyperglycaemia and put these treated diabetic mice into a cured status of diabetes.