Experimental studies of transplantation and regeneration of endocrine pancreatic cells.
Replacement of destroyed B-cells with new "healthy" ones appears to be the most physiological approach to treatment of insulin-dependent (type 1) diabetes. This could be achieved either by transplantation of isolated islets or pancreatic segments or by stimulation of the replicatory activity in the islet cells surviving the acute toxic or infectious insult. The results of our experimental investigations indicate that adult, mature insulin-producing cells can replicate very actively when challenged with a proper stimulus, such as when implanted into obese-hyperglycaemic mice. The growth of transplanted islets is, however, dependent on the site of implantation. Thus, the subcapsular space of the kidney is more favourable than the spleen. Furthermore, immunosuppressive therapy may impair islet cell replicatory activity, as demonstrated in this study for Cyclosporin A. In a search for factors stimulating islet cell replication, we found that the hepatotoxic agent galactosamine enhanced this process as observed autoradiographically one week after the injection. This fits in with previous case reports demonstrating increased mitotic activity in islets of patients suffering from various acute liver diseases. Altogether this series of experiments demonstrates that islet cell replication is a more dynamic process than has hitherto been believed. Obviously many conditions influence this process so significantly that an impact on the diabetic state of the patients can well be expected.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology; D003524:Cyclosporins / Q000494:pharmacology; D005688:Galactosamine / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000601:surgery; D051379:Mice; D008820:Mice, Obese; D012038:Regeneration; D013154:Spleen / Q000601:surgery; D013268:Stimulation, Chemical
D003524:Cyclosporins; D005688:Galactosamine