Summary
In order to establish a model for the in vivo assessment of islet function we have used the Rowett nude rat with transplantation of allogeneic and xenogeneic (mouse) islets into the renal subcapsular space following a minimal period of diabetic induction. Thirty-one nude rats were given streptozotocin and 30 became diabetic with blood glucose levels of greater than 20 mmol/l at 48 h. Rat and mouse islets were prepared by intraductal collagenase and bovine serum albumin density gradient isolation. Eight rats received transplants of freshly prepared allogeneic islets and 8 rats received transplants of 48 h cultured allogeneic islets. Seven rats received transplants of 48 h cultured mouse islets. Diabetes was reversed in all animals and all remained normoglycaemic for 21 days. Graft removal by nephrectomy resulted in hyperglycaemia in 22 out of 23 animals. Histological examination of the grafts showed a band of endocrine tissue beneath the renal capsule which stained strongly positive for insulin and there was no evidence of lymphocytic infiltration/rejection. One rat remained normoglycaemic after graft removal, which may represent recovery of the animal's own islets from the streptozotocin-induced diabetes. Control rats remained diabetic until death. In conclusion, the athymic nude rat can be used for the assessment of allogeneic and xenogeneic islet function when a short (48 h) period of streptozotocin-induced diabetes is used. This model offers a potential method for assessing in vivo function of isolated human islets.
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References
Scharp DW, Downing R, Merrell RC, Greider M (1980) Isolating the elusive islet. Diabetes 29 [suppl 1]: 19–30
Gray DWR, McShane P, Grant A, Morris PJ (1984) A method for isolation of islets of Langerhans from the human pancreas. Diabetes 33: 1055–1061
Warnock GL, Gray DWR, McShane P, Peters M, Morris PJ (1987) Survival of cryopreserved adult human pancreatic islets of Langerhans. Transplantation 44: 75–82
Sai P, Boitard C, Debray-Sachs M, Poupland A, Assan B, Hamburger J (1981) Complement-fixing islet cell antibodies from some diabetic patients after insulin release ‘in vitro’. Diabetes 30: 1051–1057
Lacy PE, Walker MM, Fink CJ (1972) Perifusion of isolated rat islets in vitro. Diabetes 21: 987–998
Festing MFW (1981) Athymic nude rats. In: Gershwin ME, Merchant B (eds) Immunological defects of laboratory animals, vol 1. Plenum Publishing Corporation, pp 267–283
Povlsen CO, Shakkebaek NE, Rygaard J, Jensen G (1974) Het- erotransplantation of human foetal organs to the mouse mutant nude. Nature 248: 247–249
Usadel KH, Schwedes U, Basiert G, Steinau U, Klempa I, Fassbinder W, Schoffling K (1980) Transplantation of human fetal pancreas. Experience in thymusaplastic mice and rats and in a diabetic patient. Diabetes 29 [Suppl 1]: 74–79
Mandel TE, Hoffman L, Collier S, Carter WM, Koulmanda M (1982) Organ culture of fetal mouse and fetal human pancreatic islets for allografting. Diabetes 31 [Suppl 1]: 39–47
Schwedes U, Kaul S, Wdowinski J, Klempa I, Bastert G and Usadel KH (1983) The use of human fetal pancreas for transplantation: experimental and clinical results. Horm Metab Res 13: 87–90
Tuch BE, Ng ABP, Jones A, Turtle JR (1984) Histologie differentiation of human felal pancreatic expiants transplanted into nude mice. Diabetes 33: 1180–1187
Andersson A, Buschard K (1977) Culture of isolated pancreatic islets: Its applications for transplantation purposes. Trans Am Soc Artif Intern Organs XXIII: 342–345
Lundgren G, Andersson A, Borg H, Buschard K, Groth CG, Gunnarsson R, Hellerslrom C, Petersson B, Ostman J (1977) Struclural and functional integrity of isolated human islets of Langerhans mainlained in tissue culture for 1–3 weeks. Trans Proc 9: 237–240
Lake SP, Anderson J, Chamberlain J, Gardner SJ, Bell PRF, James RFL (1987) Bovine serum albumin density gradient isolation of rat pancreatic islets. Transplantation 43: 805–808
Sutton R, Peters M, McShane P, Gray DWR, Morris PJ (1986) Isolation of rat pancreatic islets by duclal injection of collagenase. Transplantation 42: 689–691
Hetherington CM, Hegan MA (1975) Breeding nude (nu/nu) mice. Lab Animals 9: 19–20
Buschard K and Rygaard J (1976) Restilution of streptozotocin induced diabetes in nude mice with pancreatic grafts from the rat. Acte Pathol Microbiol Scand Sect C 84: 221–226
Tuch BE, Jones A, Turtle JR (1985) Maturation of the response of human foetal pancreatic expiant to glucose. Diabetologia 28: 28–31
Ballinger WF, Lacy PE (1972) Transplantation of intact pancreat- ic islets in rats. Surgery 72: 175–186
Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev 22: 485–518
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Lake, S.P., Chamberlain, J., Husken, P. et al. In vivo assessment of isolated pancreatic islet viability using the streptozotocin-induced diabetic nude rat. Diabetologia 31, 390–394 (1988). https://doi.org/10.1007/BF02341509
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DOI: https://doi.org/10.1007/BF02341509