Author(s): Tamrakar AK, Schertzer JD, Chiu TT, Foley KP, Bilan PJ, et al.
Insulin resistance is associated with chronic low-grade inflammation in vivo, largely mediated by activated innate immune cells. Cytokines and pathogen-derived ligands of surface toll-like receptors can directly cause insulin resistance in muscle cells. However, it is not known if intracellular pathogen sensors can, on their own, provoke insulin resistance. Here, we show that the cytosolic pattern recognition receptors nucleotide-binding oligomerization domain-containing protein (NOD)1 and NOD2 are expressed in immune and metabolic tissues and hypothesize that their activation in muscle cells would result in cell-autonomous responses leading to insulin resistance. Bacterial peptidoglycan motifs that selectively activate NOD2 were directly administered to L6- GLUT4myc myotubes in culture. Within 3 h, insulin resistance arose, characterized by reductions in each insulin-stimulated glucose uptake, GLUT4 translocation, Akt Ser(473) phosphorylation, and insulin receptor substrate 1 tyrosine phosphorylation. Muscle cell-autonomous responses to NOD2 ligand included activation of the stress/inflammation markers c-Jun N-terminal kinase, ERK1/2, p38 MAPK, degradation of inhibitor of κBα, and production of proinflammatory cytokines. These results show that NOD2 alone is capable of acutely inducing insulin resistance within muscle cells, possibly by activating endogenous inflammatory signals and/or through cytokine production, curbing upstream insulin signals. NOD2 is hence a new inflammation target connected to insulin resistance, and this link occurs without the need of additional contributing cell types. This study provides supporting evidence for the integration of innate immune and metabolic responses through the involvement of NOD proteins and suggests the possible participation of cell autonomous immune responses in the development of insulin resistance in skeletal muscle, the major depot for postprandial glucose utilization.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/20926588
Author(s): Arab JP, Candia R, Zapata R, MuÃ±oz C, Arancibia JP, et al.
Author(s): Machado MV, Cortez-Pinto H1
Author(s): Aron-Wisnewsky J, Gaborit B, Dutour A, Clement K
Author(s): Lambert JE, Ramos-Roman MA2, Browning JD3, Parks EJ4
Author(s): Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, et al.
Author(s): Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, et al.
Author(s): Tateya S, Kim F, Tamori Y
Author(s): Gangarapu V, YÃ„Â±ldÃ„Â±z K, Ince AT, Baysal B
Author(s): Miura K, Ohnishi H1
Author(s): Machado M, Marques-Vidal P, Cortez-Pinto H
Author(s): Anstee QM, Targher G, Day CP
Author(s): Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, et al.
Author(s): Goel A, Gupta M, Aggarwal R
Author(s): Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, et al.
Author(s): Ley RE, BÃ¤ckhed F, Turnbaugh P, Lozupone CA, Knight RD, et al.
Author(s): Musso G, Gambino R, Cassader M
Author(s): Tilg H, Kaser A
Author(s): Ley RE, Turnbaugh PJ, Klein S, Gordon JI
Author(s): Schwiertz A, Taras D, SchÃ¤fer K, Beijer S, Bos NA, et al.
Author(s): Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, et al.
Author(s): Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, et al.
Author(s): BÃ¤ckhed F, Ding H, Wang T, Hooper LV, Koh GY, et al.
Author(s): BÃ¤ckhed F, Manchester JK, Semenkovich CF, Gordon JI
Author(s): Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, et al.
Author(s): Parekh PJ, Arusi E, Vinik AI2, Johnson DA3
Author(s): Shen J, Obin MS, Zhao L
Author(s): Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, et al.
Author(s): Caricilli AM, Picardi PK, de Abreu LL, Ueno M, Prada PO, et al.
Author(s): Spor A, Koren O, Ley R
Author(s): Caricilli AM, Saad MJ
Author(s): Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, et al.
Author(s): Zhao L, Hu P, Zhou Y, Purohit J, Hwang D
Author(s): Winder WW, Hardie DG
Author(s): Tilg H, Moschen AR
Author(s): Franchi L, Eigenbrod T, MuÃ±oz-Planillo R, NuÃ±ez G
Author(s): Kim KA, Gu W, Lee IA, Joh EH, Kim DH
Author(s): Rivera CA, Adegboyega P, van Rooijen N, Tagalicud A, Allman M, et al.
Author(s): Takaki A, Kawai D, Yamamoto K
Author(s): Ye D, Li FY, Lam KS, Li H, Jia W, et al.
Author(s): Miura K, Kodama Y, Inokuchi S, Schnabl B, Aoyama T, et al.
Author(s): Ehses JA, Meier DT, Wueest S, Rytka J, Boller S, et al.
Author(s): Himes RW, Smith CW
Author(s): Rivera CA, Gaskin L, Allman M, Pang J, Brady K, et al.
Author(s): Szabo G, Velayudham A, Romics L Jr, Mandrekar P
Author(s): Cario E, Gerken G, Podolsky DK
Author(s): Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, et al.
Author(s): Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, et al.
Author(s): Chen GY, Liu M, Wang F, Bertin J, NÃºÃ±ez G
Author(s): Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, et al.
Author(s): Wlodarska M, Thaiss CA2, Nowarski R3, Henao-Mejia J3, Zhang JP4, et al.
Author(s): Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J, et al.
Author(s): Kamari Y, Shaish A, Vax E, Shemesh S, Kandel-Kfir M, et al.
Author(s): Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, et al.
Author(s): Bergheim I, Weber S, Vos M, KrÃ¤mer S, Volynets V, et al.
Author(s): Gibson GR, Roberfroid MB
Author(s): Gibson GR, Probert HM, Loo JV, Rastall RA, Roberfroid MB
Author(s): Slavin J1
Author(s): Parnell JA, Raman M, Rioux KP, Reimer RA
Author(s): Macfarlane S, Macfarlane GT, Cummings JH
Author(s): Parnell JA, Reimer RA
Author(s): Daubioul C, Rousseau N, Demeure R, Gallez B, Taper H, et al.
Author(s): Levrat MA, RÃ©mÃ©sy C, DemignÃ© C
Author(s): Topping DL, Clifton PM
Author(s): Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, et al.
Author(s): Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, et al.
Author(s): Beylot M1
Author(s): Parnell JA, Reimer RA
Author(s): Sanders ME1
Author(s): Iacono A, Raso GM, Canani RB, Calignano A, Meli R
Author(s): Ma YY, Li L, Yu CH, Shen Z, Chen LH, et al.