Evidence for the presence of type I IL-1 receptors on beta-cells of islets of Langerhans

Biochim Biophys Acta. 1997 Oct 24;1361(3):313-20. doi: 10.1016/s0925-4439(97)00039-2.

Abstract

The cytokine interleukin-1beta (IL-1beta) has been shown to inhibit insulin secretion and destroy pancreatic islets by a mechanism that involves the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO). Insulin containing beta-cells, selectively destroyed during the development of autoimmune diabetes, appear to be the islet cellular source of iNOS following treatment with IL-1beta. In this study we have evaluated the presence of type I IL-1 signaling receptors on purified pancreatic beta-cells. We show that the interleukin-1 receptor antagonist protein (IRAP) prevents IL-1beta-induced nitrite formation and IL-1beta-induced inhibition of insulin secretion by isolated islets and primary beta-cells purified by fluorescence-activated cell sorting (FACS). The protective effects of IRAP correlate with an inhibition of IL-1beta-induced iNOS expression by islets and FACS purified beta-cells. To provide direct evidence to support beta-cell expression of IL-1 type I signaling receptors, we show that antiserum specific for the type I IL-1 receptor neutralizes IL-1beta-induced nitrite formation by RINm5F cells, and that RINm5F cells express the type I IL-1 receptor at the protein level. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the expression of type I IL-1 signaling receptors by FACS purified beta-cells and not alpha-cells is demonstrated. These results provide direct support for the expression of type I IL-1 receptors by primary pancreatic beta-cells, the cell type selectively destroyed during the development of autoimmune diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Flow Cytometry
  • Insulin / metabolism
  • Insulin Antagonists / pharmacology
  • Insulin Secretion
  • Interleukin 1 Receptor Antagonist Protein
  • Islets of Langerhans / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / metabolism*
  • Sialoglycoproteins / pharmacology

Substances

  • Insulin
  • Insulin Antagonists
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Interleukin-1
  • Sialoglycoproteins