GROWTH OF INTRAPORTALLY TRANSPLANTED ISLETS UNDER LIVER-REGENERATION STIMULUS AND RESTORATION OF NORMOGLYCEMIA IN STREPTOZOCIN-DIABETIC RATS

Background. Limitation of beta-cell growth after intraportal islet tra nsplantation plays an important role in graft failure. To induce trans planted beta-cell proliferation, we studied the effect of compensatory liver growth in diabetic rats that had a subtherapeutic islet mass pr eviously infected into the liver. Methods. Syngeneic rats were used an islet donors or recipients; diabetes was induced by streptozocin. The re groups of streptozocin-treated rats were studied. In group 1, 250 i slets were selectively transplanted into the posterior liver loves and 10 days later anterior portal branch ligation (PBL) was performed (n = 18); in group 2, 250 islets were transplanted into the posterior lob es and 10 days later sham PBL was performed (n = 13); in group 3, rats underwent a sham transplantation and PBL (n = 6). Nonfasting blood gl ucose levels and body weight were monitored. Six rats ingroup 1 and 2 were killed 48 hours after PBL, liver section sere stained for prolife rating cell nuclear antigen, and islet cell labeling index was calcula ted. The remaining rats were killed 30 days later. Liver compensatory growth or atrophy was calculated and morphometric determination of bet a-cell areas was assesed on insulin-immunostained sections of the live r. Results. In group 1 rats killed 48 hours after PBL, islet cell labe ling index was significantly higher than in group 2 (p < 0.001). After PBL, we observed normalization of nonfasting blood glucose levels in 10 of 12 rats. At 30 days, posterior liver loves showed compensatory g rowth (218.5% +/- 18.6%) accompanied by atrophy of the anterior lobes; morphometric study of liver-engrafted islets showed a significant inc rease of individual beta-cell area, compared with group 2 (p < 0.0001) . In groups 2 and 3 normpoglycemia was not achieved. Conclusion. In st reptozocin-diabetic rats, normoglycemia was restored after transplanta tion of a subtherapeutic iselt mass, followed by PBL-induced liver reg eneration. Histologic and morphometric results indicating islet cell p roliferation suggest that compensatory liver growth might have induced a hyertrophic/hyperplastic repsonse in the intraportally transplanted beta-cells.