title: Length of metabolic normalization after rat islet cell transplantation depends on endocrine cell composition of graft and on donor age.
abstract: In vitro studies have demonstrated that beta-cell functions are negatively influenced by age and positively by the presence of glucagon producing alpha cells. This study examines whether the function of beta-cell grafts varies with the age of the donor and with the presence of other endocrine islet cells. Islet beta and endocrine non-beta-cells were purified from 10- to 30-week-old Lewis rats, and reaggregated into pure beta and mixed endocrine cell aggregates. Grafts consisted of 1.2 to 1.7 million beta cells with or without 0.6-0.7 million alpha cells. Their intraportal transplantation in 10-week-old streptozotocin-diabetic rats corrected hyperglycaemia in all experimental groups, with normal glucose tolerance curves at post-transplantation week (PT wk) 4. Recipients of mixed endocrine cell grafts from 10-week-old donors maintained a glucose tolerant state until PT wk 20, but turned glucose intolerant thereafter; only 1 of 12 animals was overtly diabetic at PT wk 64. Recipients of pure beta-cell grafts from 10-week-old donors became glucose-intolerant from PT wk 4 on, with 5 of 11 cases developing overt diabetes before PT wk 64. When grafts were prepared from 30-week-old donors, metabolic deterioration started earlier, again with a more rapid loss for pure beta-cell grafts; at PT wk 64, virtually all recipients were overtly diabetic. It is concluded that delayed graft failure can be the consequence of an insufficient number of islet endocrine non-beta-cells as well as of a higher donor age. This observation can explain late failures in animal and human islet transplantation using marginally low beta-cell numbers. The interpretation of long-term studies on islet cell transplantation can benefit from the use of standardized grafts with well defined cellular composition.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Keymeulen
authors.forename: J
authors.initials: J
authors.lastname: Anselmo
authors.forename: D
authors.initials: D
authors.lastname: Pipeleers
mesh_terms: D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000601:surgery*; D019270:Fructosamine / Q000097:blood; D005934:Glucagon / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019270:Fructosamine; D005934:Glucagon