title: Convergence of innate immunity and insulin resistance as evidenced by increased nucleotide oligomerization domain (NOD) expression and signaling in monocytes from patients with type 2 diabetes.
abstract: Despite the well known role of nucleotide oligomerization domain (NOD) receptor proteins in innate immunity, their association with diabetes is less explored. Here we report the transcriptional level of NODs and their downstream molecular signatures in CD14(+) monocytes from subjects with different grades of glucose tolerance. NOD1 and NOD2 mRNA expression were significantly up-regulated in monocytes from patients with type 2 diabetes (T2DM) and positively correlated with HOMA-IR and poor glycemic control. Patients with T2DM also exhibited increased monocyte activation markers (CD11b and CD36) and proinflammatory signals downstream of NOD (RIPK2 and NFκB) along with the increased circulatory levels of TNF-α and IL-6. In vitro stimulation of monocytes with NOD specific ligands-i-EDAP and MDP significantly up regulated the mRNA expression of NOD1 and NOD2 respectively in T2DM. Our study exposes up regulation of NODs in monocytes as an important component of inflammation and insulin resistance in patients with T2DM.
authors.affiliation: Department of Cell and Molecular Biology, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Shiny
authors.forename: Bhaskaran
authors.initials: B
authors.lastname: Regin
authors.forename: Venketesan
authors.initials: V
authors.lastname: Balachandar
authors.forename: Kuppan
authors.initials: K
authors.lastname: Gokulakrishnan
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Balasubramanyam
mesh_terms: D000328:Adult; D039481:CD11b Antigen / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018955:CD36 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; D014157:Transcription Factors; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D005947:Glucose
keywords: HOMA; HbA1C; IGT; IL-6; Inflammation; Innate immunity; Insulin resistance; MDP; NFκβ; NGT; NOD; Nucleotide oligomerization domain (NOD); OR; PGN; PRR; RIPK2; T2DM; TLR; TNF-α; Type 2 diabetes; glycated hemoglobin; homeostasis assessment model; iEDAP; impaired glucose tolerance; interleukin-6; muramyl dipeptide; normal glucose tolerance; nuclear factor kappa beta; nucleotide binding oligomerization domain; odds ratio; pattern recognition receptor; peptidoglycan; receptor interacting protein kinase 2; toll like receptor; tumor necrosis factor – alpha; type 2 diabetes mellitus; γ-d-glutamyl-meso diaminopimelic acid
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