Document Detail

Length of metabolic normalization after rat islet cell transplantation depends on endocrine cell composition of graft and on donor age.
MedLine Citation:
PMID:  9349595     Owner:  NLM     Status:  MEDLINE    
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.
B Keymeulen; J Anselmo; D Pipeleers
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetologia     Volume:  40     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1998-01-15     Completed Date:  1998-01-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1152-8     Citation Subset:  IM    
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
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MeSH Terms
Age Factors
Blood Glucose / metabolism
Body Weight
Diabetes Mellitus, Experimental / metabolism*,  surgery*
Fructosamine / blood
Glucagon / metabolism
Graft Survival / physiology*
Insulin / metabolism
Islets of Langerhans Transplantation / methods*
Liver / metabolism
Pancreas / metabolism
Rats, Inbred Lew
Time Factors
Reg. No./Substance:
0/Blood Glucose; 11061-68-0/Insulin; 4429-04-3/Fructosamine; 9007-92-5/Glucagon

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