PROLIFERATION AND HYPERTROPHY OF LIVER-CELLS SURROUNDING ISLET GRAFTSIN DIABETIC RECIPIENT RATS

The liver offers an adequate site for the metabolic function of pancre atic islet implants. Little is known about the effects of the islet gr afts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following in traportal injection of syngeneic islets. Implantation of 800-islet-gra fts, containing 0.9 million beta cells, normalized overt diabetes with in 14 days. This period of metabolic normalization was characterized b y a specific sequence of alterations in the implant area During the fi rst days after transplantation, islet cells migrated into the liver lo bules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and h ypertrophy (cellular profile area 603 +/- 72 mu m(2) in diabetic islet recipients vs. 382 +/- 42 mu m(2) in diabetic controls; P <.005). The implant area also contained significantly more liver cells in prolife rative activity than hepatic tissue in normal controls (bromodeoxyurid ine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on p osttransplantation days 2, 4, and 14, respectively, compared with 0.02 % in normal controls). The cellular hypertrophy and hyperplasia explai n the sudden increase in Liver weight of diabetic recipients (from 8.0 +/- 1.1 g to 13.8 +/- 2.2 g on posttransplantation day 2; P <.005). B oth alterations can be attributed to the massive local discharge of in sulin in an insulin-deficient organ containing an excess of extracellu lar nutrients. Progressive revascularization of the implant sites and overall metabolic normalization are thought to explain the return of a normal Liver histology by the third week after transplantation. In co nclusion, intraportalislet grafts exert profound effects on the liver of diabetic rat recipients. The morphological features of the implant sites may serve as markers for the function of the islet grafts as wel l as for the adaptive capacity of the recipient liver.