TY - JOUR

T1 - Genetically determined differences in newborn rat islet sensitivity to interleukin-1 in vitro

T2 - no association with the diabetes prone phenotype in the BB-rat

AU - Andersen, H U

AU - Mandrup-Poulsen, T

AU - Egeberg, J

AU - Helqvist, S

AU - Nerup, J

PY - 1989/1

Y1 - 1989/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cells, Cultured

KW - DNA

KW - Diabetes Mellitus, Type 1

KW - Insulin

KW - Interleukin-1

KW - Islets of Langerhans

KW - Phenotype

KW - Rats

KW - Rats, Inbred BB

KW - Rats, Inbred BN

KW - Rats, Inbred Lew

KW - Rats, Inbred Strains

KW - Rats, Inbred WF

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

VL - 120

SP - 92

EP - 98

JO - Acta Endocrinologica

JF - Acta Endocrinologica

SN - 0001-5598

IS - 1

ER -