Metabolic function of intraportal and intrasplenic islet autografts in cynomolgus monkeys.
Intraportal islet autografting can restore near-normal glucose homeostasis in large diabetic animals, but the long-term failure rate of such grafts remains high. To assess the effect of the site of transplantation, we compared the hormonal responses to glucose (500 mg/kg i.v.) of intraportal (IP) and intrasplenic (IS) islet autografts in the cynomolgus monkey previously rendered diabetic by total pancreatectomy. Intravenous glucose tolerance tests (IVGTTs) 6 wk after IP grafting (n = 10) demonstrated nearly normal plasma glucose changes, with qualitatively normal but quantitatively reduced insulin and glucagon responses; only two animals have maintained these responses for greater than 2 yr. IVGTTs 6 wk after IS grafting (n = 4) demonstrated more abnormal plasma glucose changes, with qualitatively normal but weak insulin responses and glucagon levels that did not fall in response to hyperglycemia; only one animal has maintained fasting normoglycemia for greater than 9 mo. These results suggest that IS transplantation confers no benefit over IP transplantation in this model.
Sutton
R
R
Nuffield Department of Surgery, John Radcliffe Hospital, Headington, Oxford, UK.
Gray
D W
DW
Burnett
M
M
McShane
P
P
Turner
R C
RC
Morris
P J
PJ
D000818:Animals; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008252:Macaca fascicularis; D008297:Male; D013154:Spleen
D007328:Insulin; D005934:Glucagon