Glucose activation of islets of Langerhans up-regulates Toll-like receptor 5: possible mechanism of protection

Christian Roar Andersen Weile, Knud Elnegaard Josefsen, Karsten Stig Buschard

6 Citations (Scopus)

Abstract

Toll-like receptors are pattern-recognition receptors of the innate immune system that are activated during viral, bacterial or other infections, as well as during disease progression of type 1 and type 2 diabetes. Toll-like receptor 5 (TLR-5) specifically recognizes bacterial infection through binding of flagellin from pathogenic bacteria such as Salmonella and Listeria species. We have found that the expression of TLR5 is up-regulated by glucose activation of isolated islets of Langerhans, in contrast to other investigated TLRs (TLR-2, -3, -4, -6 and -9. Stimulation of islets with 10 mm glucose increased the levels of TLR5 mRNA 10-fold (P=0·03) and the TLR-5 protein levels twofold (P=0·04). Furthermore, the protein level of downstream signalling molecule myeloid differentiation primary response gene 88 (MyD88) increased 1·6-fold (P=0·01). Activation of TLR-5 in islets lead to a marked reduction of both stimulated and basal secretion of insulin, as well as an increase in production of nitric oxide, proinflammatory cytokines, anti-inflammatory heat-shock protein and major histocompatibility complex (MHC) class I transporter. We observe no effects of TLR-5 activation on islet survival. We suggest that this regulation by TLR-5 might be beneficial during serious infection such as sepsis by limiting the activity of beta cells during peaks of insulin demand to counteract beta cell damage.
Original languageEnglish
JournalClinical and Experimental Immunology
Volume166
Issue number2
Pages (from-to)251-7
Number of pages7
ISSN0009-9104
DOIs
Publication statusPublished - 2011

Keywords

  • Animals
  • Cell Line, Tumor
  • Cytokines
  • Glucose
  • Heat-Shock Proteins
  • Inflammation
  • Insulin
  • Islets of Langerhans
  • Major Histocompatibility Complex
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Differentiation Factor 88
  • Nitric Oxide
  • RNA, Messenger
  • Rats
  • Rats, Inbred Lew
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 5

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