METABOLIC CONTROL IN STREPTOZOTOCIN-DIABETIC RATS FOLLOWING TRANSPLANTATION OF MICROENCAPSULATED PANCREATIC-ISLETS

Microencapsulated islet grafts implanted into the peritoneal cavity of a variety of animal models of diabetes have been shown to reverse hyp erglycaemia over prolonged periods without immunosuppression. Here, ef fects of these grafts on intermediary metabolites, diurnal blood gluco se and glycated haemoglobin were studied in streptozotocin-diabetic Wi star rats. Following transplantation (approximately 3000-islets) gluco se and the ketone 3-hydroxybutyrate fell significantly (glucose: 19.1 +/- 0.6 (SD) to 9.2 +/- 4.3 mmol/l, p<0.01; 3-hydroxybutyrate: 1.51 +/ - 0.48 to 0.55 +/- 0.38 mmol/l, p<0.02) and remained within/close to t he normal range for at least four weeks. In control diabetic animals, values remained abnormally elevated. There was no difference in lactat e, alanine or glycerol between the two groups. In transplanted animals there was a marked variation in blood glucose over a 24 h period, val ues being low during daylight hours but with nocturnal peaks (up to 25 mmol/1) during the animals' normal feeding time. Glycated haemoglobin was also lower in transplanted animals but did not return to normal a nd the difference was not significant. In conclusion, microencapsulate d islet grafts ameliorated the diabetic state. However, normal metabol ic homeostasis was not achieved. The intraperitoneal site precludes di rect graft vascular access and this may be a contributory factor. Addi tionally, daytime blood sugar values in murine models of diabetes may be a poor guide to graft function and glucose tolerance.