Permselective tubular membranes (1 mm i.d.) were filled with fragments of nine freshly resected human insulinomas, closed at both ends, and implanted in the peritoneal cavity of 30 streptozocin-induced diabetic rats. In 14 animals, nonfasting plasma glucose (PG) and insulin levels were normalized by these immunoprotected transplants for up to 1 yr (PG from 520 ± 12 to 142 ± 3 mg/100 ml; insulin from 6 ± 0.5 to 44 ± 3 μU/ml). These animals showed the same weight gain after 12 mo of observation as 20 controls. The remaining 16 animals showed an incomplete or transient correction of their diabetes and survived 4–6 mo, versus <8 wk in untreated animals. Removal of the membraneencapsulated insulin-secreting tissue from 8 successfully treated rats led to hyperglycemia and death within 10 days. Histology and electron microscopy of insulinoma tissue retrieved after long-term implantation showed functionally active endocrine cells and no evidence of graft rejection. In vitro perifusion gave similar results for encapsulated and nonencapsulated insulinoma tissue. The amount of insulin secreted was quite variable, and responsiveness of the insulinoma to changes in glucose concentration of the surrounding medium was observed in three out of the five tumors studied. These observations establish the effectiveness of immunoseparation by a synthetic membrane in a pancreatic xenograft model.
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Original Contribution|
June 01 1986
Long-Term Plasma Glucose Normalization in Experimental Diabetic Rats With Macroencapsulated Implants of Benign Human Insulinomas
J J Altman;
J J Altman
Service de Diabétologie, Hotel-Dieu Hospital
Paris, France
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D Houlbert;
D Houlbert
Service de Diabétologie, Hotel-Dieu Hospital
Paris, France
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P Callard;
P Callard
Service d'Anatomie Pathologique, Jean Verdier Hospital
Bondy, France
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P McMillan;
P McMillan
Division of Biology and Medicine, Brown University
Providence, Rhode Island
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B A Solomon;
B A Solomon
Amicon Corporation
Lexington, Massachusetts
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J Rosen;
J Rosen
Johnson & Johnson
New Brunswick, New Jersey
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P M Galletti
P M Galletti
Division of Biology and Medicine, Brown University
Providence, Rhode Island
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Address reprint requests to Pierre M. Galletti, M.D., Ph.D., Division of Biology and Medicine, Brown University, Providence, Rl 02912.
Diabetes 1986;35(6):625–633
Article history
Received:
March 15 1985
Revision Received:
January 03 1986
PubMed:
3011571
Citation
J J Altman, D Houlbert, P Callard, P McMillan, B A Solomon, J Rosen, P M Galletti; Long-Term Plasma Glucose Normalization in Experimental Diabetic Rats With Macroencapsulated Implants of Benign Human Insulinomas. Diabetes 1 June 1986; 35 (6): 625–633. https://doi.org/10.2337/diab.35.6.625
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