LONG-TERM METABOLIC CONTROL BY RAT ISLET GRAFTS DEPENDS ON THE COMPOSITION OF THE IMPLANT

Citation
B. Keymeulen et al., LONG-TERM METABOLIC CONTROL BY RAT ISLET GRAFTS DEPENDS ON THE COMPOSITION OF THE IMPLANT, Diabetes, 45(12), 1996, pp. 1814-1821
Citations number
26
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
00121797
Volume
45
Issue
12
Year of publication
1996
Pages
1814 - 1821
Database
ISI
SICI code
0012-1797(1996)45:12<1814:LMCBRI>2.0.ZU;2-Z
Abstract
This study examines whether the loss of metabolic control in initially normalized islet transplants can result from the inadequate compositi on of the donor tissue. Streptozotocin-induced diabetic rats were foll owed for 64 weeks after the intraportal injection of islet isografts w ith different composition. The implantation of 2.3 million beta-cells (10(7)/kg body wt) as particles (>100 pm diameter) of primarily insuli n-positive (70%) and glucagon-positive (20%) cells succeeded in a long -term normalization of 2-h fasting glycemia, glucose tolerance, and se rum fructosamine. The same metabolic control was achieved in animals w ith short and long durations of diabetes or when grafts were implanted under the kidney capsule. At posttransplantation (PT) week 64, insuli n reserves were 60% lower than those in age-matched controls, which ma y account for the glucose intolerance in a few old recipients. The sam e type of graft containing 0.7 million beta-cells (4 x 10(6)/kg body w t) corrected these metabolic parameters for more than 12 weeks; the pr oportionally lower insulin reserves were sufficient for the long-term correction of 2-h fasting glycemia, but did not avoid glucose intolera nce in older recipients. When the higher beta-cells number (10(7)/kg b ody wt) was injected as smaller particles (<100 mu m diameter) of lowe r purity (55% insulin-positive) and negligible glucagon content (<5% g lucagon-positive), the metabolic parameters were also corrected for 12 weeks PT but then progressively returned to overt diabetes (6 of 10) or glucose intolerance (4 of 10). We concluded that long-term metaboli c normalization can be achieved by islet implants in the liver or unde r the kidney capsule. The loss of metabolic control in older animals c an be caused by the inadequate composition of the graft, with the numb er of beta-cells, the proportion of other endocrine and nonendocrine c ells, and the particle size as influential variables.