Metabolic Control in Streptozotocin Diabetic Rats Following Transplantation of Microencapsulated Pancreatic Islets

 

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Summary

Microencapsulated islet grafts implanted into the peritoneal cavity of a variety of animal models of diabetes have been shown to reverse hyperglycaemia over prolonged periods without immunosuppression. Here, effects of these grafts on intermediary metabolites, diurnal blood glucose and glycated haemoglobin were studied in streptozotocin-diabetic Wistar rats. Following transplantation (approximately 3000 islets) glucose 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 the normal range for at least four weeks. In control diabetic animals, values remained abnormally elevated. There was no difference in lactate, alanine or glycerol between the two groups. In transplanted animals there was a marked variation in blood glucose over a 24 h period, values being low during daylight hours but with nocturnal peaks (up to 25 mmol/l) during the animals' normal feeding time. Glycated haemoglobin was also lower in transplanted animals but did not return to normal and the difference was not significant. In conclusion, microencapsulated islet grafts ameliorated the diabetic state. However, normal metabolic homeostasis was not achieved. The intraperitoneal site precludes direct graft vascular access and this may be a contributory factor. Additionally, daytime blood sugar values in murine models of diabetes may be a poor guide to graft function and glucose tolerance.