Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islet allografts.
Albino Oxford rats made diabetic with 75 mg/kg streptozotocin were intraperitoneally transplanted with 2500-2900 alginate-polylysine microencapsulated Lewis islets (n = 9, total islet tissue volume 8.0-11.0 microliters), or a similar volume of non-encapsulated Lewis islets (n = 5). All rats with microencapsulated islets became normoglycaemic, and remained normoglycaemic for 5-16 weeks. In rats with non-encapsulated islet grafts, only a temporary decrease in blood glucose was observed, and all were again severely hyperglycaemic at 1 week after implantation. At 5-6 weeks after transplantation, glucose tolerance in rats with microencapsulated islets was tested by intravenous glucose infusion (10 mg/min over 20 min) and test meal administration (n = 4). During glucose infusion, maximum glucose levels were 13.0 +/- 0.4 mmol/l in rats with microcapsules and 8.9 +/- 0.4 mmol/l in healthy control rats (p less than 0.01). Concomitant maximum plasma insulin levels were 215 +/- 17 pmol/l in rats with microcapsules and 715 +/- 85 pmol/l in controls (p less than 0.001). After the test meal, maximum blood glucose was 10.6 +/- 0.9 mmol/l in rats with microcapsules and 6.2 +/- 0.1 mmol/l in controls (p less than 0.001), with concomitant maximum plasma insulin levels of 247 +/- 11 pmol/l and 586 +/- 59 pmol/l, respectively (p less than 0.001). In conclusion, although the glucose tolerance is impaired and plasma insulin responses to intravenous glucose-load and test-meal are reduced, the alginate-polylysine membrane does provide adequate immunoisolation for the prolongation of allograft survival, resulting in prolonged normoglycaemia in streptozotocin diabetic rats.
Department of Surgery, University of Groningen, The Netherlands.
W M
WM
Fritschy
J H
JH
Strubbe
G H
GH
Wolters
R
R
van Schilfgaarde
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D004435:Eating; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000473:pathology / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous
D001786:Blood Glucose; D007328:Insulin