RGD Reference Report - Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syngeneically transplanted islets, and improves metabolic outcome. - Rat Genome Database

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Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syngeneically transplanted islets, and improves metabolic outcome.

Authors: Tellez, N  Montolio, M  Estil-les, E  Escoriza, J  Soler, J  Montanya, E 
Citation: Tellez N, etal., Diabetologia. 2007 Mar;50(3):602-11. Epub 2007 Jan 13.
RGD ID: 8551855
Pubmed: PMID:17221214   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-006-0548-1   (Journal Full-text)

AIMS/HYPOTHESIS: Interleukin-1 receptor antagonist (IL1RN, also known as IL1RA) is a naturally occurring inhibitor of IL-1 action and its overproduction protects pancreatic islets from the deleterious effects of IL-1beta on beta cell replication, apoptosis and function. The aim of this study was to determine whether viral gene transfer of the Il1rn gene into rat islets ex vivo had a beneficial effect on the outcome of the graft. MATERIALS AND METHODS: Streptozotocin-diabetic Lewis rats were syngeneically transplanted with 500 or 800 Ad-Il1rn-infected or uninfected islets. Islet grafts were collected on day 3, 10 or 28 after transplantation and beta cell apoptosis, replication, size and mass were determined. RESULTS: Animals transplanted with 500 islets remained hyperglycaemic throughout the follow-up, as expected. Beta cell replication increased in the Ad-Il1rn group on days 3, 10 and 28 after transplantation compared with normal pancreas. In uninfected islets, by contrast, beta cell replication was increased only on day 10. Beta cell apoptosis was increased in all transplanted groups; it was 25% lower in the Ad-Il1rn than in uninfected groups, but differences were not statistically significant. The initially transplanted beta cell mass was reduced on day 3, increasing subsequently in Ad-Il1rn grafts, but not in uninfected grafts. When 800 islets were transplanted, all animals grafted with Ad-Il1rn-infected islets, but only 40% of those transplanted with uninfected islets, achieved normoglycaemia 14 days after transplantation. CONCLUSIONS/INTERPRETATION: Overproduction of IL1RN increased beta cell replication and mass of islet grafts and reduced the beta cell number required to achieve normoglycaemia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  IMP 8551855human gene in a rat modelRGD 
Experimental Diabetes Mellitus  ISOIL1RN (Homo sapiens)8551855; 8551855human gene in a rat modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Mus musculus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Homo sapiens)
IL1RN  (interleukin 1 receptor antagonist)


Additional Information