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

Clin Exp Immunol. 2011 Nov;166(2):251-7. doi: 10.1111/j.1365-2249.2011.04457.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cytokines
  • Heat-Shock Proteins
  • Insulin
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Toll-Like Receptor 5
  • Nitric Oxide
  • Glucose