Genetically determined differences in newborn rat islet sensitivity to interleukin-1 in vitro: no association with the diabetes prone phenotype in the BB-rat.
This study was designed to investigate whether the genetic predisposition to insulin-dependent diabetes mellitus (IDDM) might be caused by an inherited increased sensitivity of the pancreatic B-cells to immune effector molecules e.g. the monokine interleukin 1 (IL-1), which is selectively cytotoxic to B-cells in vitro. Islets of Langerhans isolated from newborn diabetes prone and diabetes resistant Bio-Breeding rats, as well as from the inbred non-diabetic rat strains Wistar Furth, Brown-Norway and Lewis-Scripps were exposed to 0-1000 ng/l [corrected] of recombinant human IL-1 beta for 7 days. Strain-related differences in the sensitivity to IL-1 were studied by comparing the dose-responses of insulin release at 11 mmol/l glucose and islet light microscopic morphology to varying concentrations of IL-1. Statistical analyses showed a significant impact of strain on B-cell sensitivity to IL-1, Brown-Norway islets being relatively resistant to the action of IL-1. However, the the diabetes prone islets were not more sensitive to the cytotoxic effect of IL-1 than the non-diabetic control strain islets. We conclude that genetic differences in the response to IL-1 exist in vitro, but that this phenomenon is unrelated to the propensity to develop IDDM.
Andersen
H U
HU
Steno Memorial Hospital, Gentofte, Denmark.
Mandrup-Poulsen
T
T
Egeberg
J
J
Helqvist
S
S
Nerup
J
J
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB / Q000235:genetics*; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains / Q000235:genetics*; D011920:Rats, Inbred WF
D007328:Insulin; D007375:Interleukin-1; D004247:DNA