Pancreatic Islet Isotransplantation: Effects of Age and Organ Culture of Donor Islets on Reversal of Diabetes in Rats

Pancreatic islets were isolated by identical collagenase digestion from two groups of Wistar-Lewis rats, of both sexes, according to body weight: I, or young and <200 gm., and II, or old and >400 gm. These islets were transplanted into 27 male rats that had streptozotocin-induced hyperglycemia and a fasting plasma glucose of 350 to 400 mg./dl. Thirteen of the rats received islets from group I (1,000 islets per rat injected into the portal vein), nine of which responded promptly with a drop in plasma glucose to less than ISO mg./dl. that was sustained for the remaining 12 months of the study. Fourteen were recipients of old-group islets, and none had a lowering of plasma glucose. Ultrastructural and functional analyses of freshly isolated islets of young and old donors revealed them to be identical. Histology of livers of recipients six weeks after transplantation showed numerous well-granulated islets in responded but no islet tissue in nonresponders. An investigation of membrane characteristics of islets of young and old donors, with concanavalin A (Con A) binding used as a probe, showed that freshly isolated islets of both young and old donors were unable to bind Con A. However, islets of young donors could bind Con A after storage in tissue culture medium 199 for one hour, whereas islets of old donors required at least four hours of maintenance before the capacity to bind Con A could be demonstrated. Ability of islets of young and old donors to bind Con A appeared to correlate with the capacity of the islets to survive and to induce normoglycemia after intraportai injection into isogeneic recipients.