title: Glucose activation of islets of Langerhans up-regulates Toll-like receptor 5: possible mechanism of protection.
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.
authors: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark. cweile@yahoo.dk
authors: C
authors: C
authors: Weile
authors: K
authors: K
authors: Josefsen
authors: K
authors: K
authors: Buschard
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006360:Heat-Shock Proteins; D007328:Insulin; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D051198:Toll-Like Receptor 5; D009569:Nitric Oxide; D005947:Glucose