TY - JOUR
T1 - Proliferation and hypertrophy of liver cells surrounding islet grafts in diabetic recipient rats
AU - De Paepe, Monique E.
AU - Keymeulen, Bart
AU - Pipeleers, Daniel
AU - Klöppel, Günter
N1 - Funding Information:
Abbreviations: STZ, streptozotocin; BrdU, 5'-bromo-2'-deoxyuridine; PAS, periodic acid-Schiff. From the Departments of ~Experimental Pathology and 2Endocrinology and Metabolism, Free University of Brussels, Brussels, Belgium. Received June 22, 1994; accepted November 16, 1994. Supported by grants from the Belgian National Research Council (F.G.W.O. nes. 3.0093.90 and 3.0057.94, Brussels, Belgium). This study has been performed within the framework of the concerted action "Treatment of diabetes by islet cell transplantation" of the European Community Medical and Health Research Program. Address reprint requests to: Professor Dr Giinter K15ppeI, Department of Experimental Pathology, Free University of Brussels (Jette), Laarbeeklaan 103, B 1090 Brussels, Belgium. Copyright © 1995 by the American Association for the Study of Liver Diseases. 0270-9139/95/2104-003753.00/0
PY - 1995/4
Y1 - 1995/4
N2 - The liver offers an adequate site for the metabolic function of pancreatic islet implants. Little is known about the effects of the islet grafts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following intraportal injection of syngeneic islets. Implantation of 800-islet-grafts, containing 0.9 million beta cells, normalized overt diabetes within 14 days. This period of metabolic normalization was characterized by a specific sequence of alterations in the implant area. During the first days after transplantation, islet cells migrated into the liver lobules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and hypertrophy (cellular profile area 603 ± 72 μm2 in diabetic islet recipients vs. 382 ± 42 μm2 in diabetic controls; P < .005). The implant area also contained significantly more liver cells in proliferative activity than hepatic tissue in normal controls (bromodeoxyuridine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on posttransplantation days 2, 4, and 14, respectively, compared with 0.02% in normal controls). The cellular hypertrophy and hyperplasia explain the sudden increase in liver weight of diabetic recipients (from 8.0 ± 1.1 g to 13.8 ± 2.2 g on post-transplantation day 2; P < .005). Both alterations can be attributed to the massive local discharge of insulin in an insulin-deficient organ containing an excess of extra-cellular 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 conclusion, intraportal islet 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 well as for the adaptive capacity of the recipient liver.
AB - The liver offers an adequate site for the metabolic function of pancreatic islet implants. Little is known about the effects of the islet grafts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following intraportal injection of syngeneic islets. Implantation of 800-islet-grafts, containing 0.9 million beta cells, normalized overt diabetes within 14 days. This period of metabolic normalization was characterized by a specific sequence of alterations in the implant area. During the first days after transplantation, islet cells migrated into the liver lobules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and hypertrophy (cellular profile area 603 ± 72 μm2 in diabetic islet recipients vs. 382 ± 42 μm2 in diabetic controls; P < .005). The implant area also contained significantly more liver cells in proliferative activity than hepatic tissue in normal controls (bromodeoxyuridine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on posttransplantation days 2, 4, and 14, respectively, compared with 0.02% in normal controls). The cellular hypertrophy and hyperplasia explain the sudden increase in liver weight of diabetic recipients (from 8.0 ± 1.1 g to 13.8 ± 2.2 g on post-transplantation day 2; P < .005). Both alterations can be attributed to the massive local discharge of insulin in an insulin-deficient organ containing an excess of extra-cellular 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 conclusion, intraportal islet 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 well as for the adaptive capacity of the recipient liver.
UR - http://www.scopus.com/inward/record.url?scp=0028955951&partnerID=8YFLogxK
U2 - 10.1016/0270-9139(95)90267-8
DO - 10.1016/0270-9139(95)90267-8
M3 - Article
C2 - 7705790
AN - SCOPUS:0028955951
SN - 0270-9139
VL - 21
SP - 1144
EP - 1153
JO - Hepatology
JF - Hepatology
IS - 4
ER -
