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  • Author: Henrik Ullits Andersen x
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Steffen Helqvist, Pierre Bouchelouche, Henrik Ullits Andersen and Jørn Nerup

Abstract.

The controlled flux of calcium across the cell membrane is intimately linked to the release of insulin from pancreatic beta-cells, but the uncontrolled influx of calcium is a common final denominator of cell death. Because interleukin 1 has been shown to be cytotoxic to beta-cells in isolated rat islets of Langerhans and since interleukin 1 has a calcium ionophore effect on other cell types, this study was designed to test whether alterations of the calcium flux across the beta-cell membrane would influence the effects of interleukin 1 on isolated rat and mouse islets. Further, the cytosolic free Ca2+ concentration was measured by the fura-2 method in rat islets during acute interleukin 1 exposure. Treatment with 10 μmol/l of verapamil (a potent blocker of the voltage-dependent calcium channel) tended to suppress the inhibitory effect of interleukin 1 on insulin release from rat islets, suggesting protection against cytotoxicity. Conversely, a stimulatory effect of interleukin 1 on mouse islets during 6 days of exposure to interleukin 1 was turned into inhibition by high extracellular calcium concentration. Interleukin 1 did not have any acute effect on cytosolic free Ca2+ concentration. In conclusion, interleukin 1 has no specific calcium ionophore effect on beta-cells, but alterations of the calcium flux across the beta-cell membrane influence the functional effects of interleukin 1, suggesting interference with cell function and toxicity, which would likely be accompanied by an uncontrolled influx of calcium.

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Henrik Ullits Andersen, Thomas Mandrup-Poulsen, Jørn Egeberg, Steffen Helqvist and Jørn Nerup

Abstract. 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 fg/1 of recombinant human IL-1 β 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.

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Henrik Ullits Andersen, Thomas Mandrup-Poulsen, Jørn Egeberg, Steffen Helqvist and Jørn Nerup

Acta Endocrinologica (Copenh) 1989, 120: 92–98

Interleukin-1 concentration should read ng/l instead of fg/1.

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Steffen Helqvist, Birgit Sehested Hansen, Jesper Johannesen, Henrik Ullits Andersen, Jens Høiriis Nielsen and Jørn Nerup

Abstract.

It is hypothesized that interleukin 1 induces toxic free radical formation in pancreatic beta-cells leading to beta-cell degeneration and destruction. Therefore, isolated rat pancreatic islets were examined for interleukin 1 and heat shock induced proteins. After exposure to human interleukin 1β (0.015 to 10 μg/1) or heat (40°C) for up to 24 h, islets were labelled with 35S-methionine and solubilized. Islets proteins were analysed by SDS-polyacrylamide gel electrophoresis. By autoradiography it was shown that both interleukin 1 and heat exposure induced the formation of a 70 kD protein. Further, interleukin 1 induced the formation of two proteins of 32 and 80 kD, respectively, which was not seen after heat exposure. Possibly, the 70 kD protein is a member of the heat shock protein 70 family, participating in unspecific cellular defence and maybe free radical scavenging. Other candidates are the superoxide radical scavenging enzyme manganous superoxidedismutase, MHC class II molecules, and heme oxygenase.