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.
Key words
Microencapsulation - Islets of Langerhans - Transplantation - Streptozotocin Diabetic
Rat
