Correlation analysis of monocyte subsets and insulin resistance considering fetuin-A involvement in patients with type 2 diabetes
Tóm tắt
Fetuin-A is a multifunctional circulating glycoprotein that can induce insulin resistance. Lately, adipose tissue has gained prominence as an effector site of fetuin-A. Although fetuin-A—induced proinflammatory polarization and migration of macrophages plays a crucial role, it remains obscure whether monocyte subsets in circulation could simulate characteristics of macrophages in adipose tissues. This study aims to investigate the correlation between monocyte subsets with fetuin-A and its relevant insulin resistance. We evaluated serum fetuin-A levels in 107 patients with type 2 diabetes (T2D). Using flow cytometry, we classified monocyte subsets into three subtypes: (a) classical, CD14++CD16−; (b) intermediate, CD14++CD16+, the most proinflammatory one; (c) and nonclassical, CD14+CD16++. We assessed the insulin resistance by the homeostasis model assessment for insulin resistance (HOMA-IR) in 68 patients without insulin injections. We observed no correlation between fetuin-A levels and classical (ρ = − 0.005; P = 0.959), intermediate (ρ = 0.022; P = 0.826), and nonclassical monocyte counts (ρ = 0.063; P = 0.516), respectively. In addition, no significant correlation was found between log (HOMA-IR) and classical (ρ = 0.052; P = 0.688), intermediate (ρ = 0.054; P = 0.676), and nonclassical monocyte counts (ρ = 0.012; P = 0.353), respectively. However, serum fetuin-A levels showed positive correlation with log (HOMA-IR) (ρ = 0.340; P = 0.007). Multiple regression analyses revealed a significant relationship between fetuin-A and log (HOMA-IR) (β = 0.313; P = 0.016), but not with monocyte subsets. Monocyte subsets in circulation, including proinflammatory intermediate monocytes, were not associated with fetuin-A and insulin resistance.
Tài liệu tham khảo
Mori K, Emoto M, Inaba M (2011) Fetuin-A: a multifunctional protein. Recent Pat Endocr Metab Immune Drug Discov 5(2):124–146
Stefan N, Haring HU (2013) The role of hepatokines in metabolism. Nat Rev Endocrinol 9(3):144–152
Mori K, Emoto M, Inaba M (2012) Fetuin-A and the cardiovascular system. Adv Clin Chem 56:175–195
Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S et al (2012) Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18(8):1279–1285
Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S et al (2013) Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. J Biol Chem 288(39):28324–28330
Heine GH, Ortiz A, Massy ZA, Lindholm B, Wiecek A, Martinez-Castelao A et al (2012) Monocyte subpopulations and cardiovascular risk in chronic kidney disease. Nat Rev Nephrol 8(6):362–369
Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN et al (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116(16):e74–e80
Yang J, Zhang L, Yu C, Yang XF, Wang H (2014) Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark Res 2(1):1
Heine GH, Ulrich C, Seibert E, Seiler S, Marell J, Reichart B et al (2008) CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients. Kidney Int 73(5):622–629
Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D et al (2011) CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J 32(1):84–92
Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P et al (2012) CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 60(16):1512–1520
American Diabetes A (2004) Diagnosis and classification of diabetes mellitus. Diabetes Care 27(Suppl 1):S5–S10
Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y et al (2007) Modification of the modification of diet in renal disease (MDRD) study equation for Japan. Am J Kidney Dis 50(6):927–937
Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H et al (2006) Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 29(2):468
Mori K, Emoto M, Araki T, Yokoyama H, Lee E, Teramura M et al (2008) Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus. Metabolism 57(9):1248–1252
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419
Rogacev KS, Ulrich C, Blomer L, Hornof F, Oster K, Ziegelin M et al (2010) Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J 31(3):369–376
Poitou C, Dalmas E, Renovato M, Benhamo V, Hajduch F, Abdennour M et al (2011) CD14dimCD16+ and CD14+CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis. Arterioscler Thromb Vasc Biol 31(10):2322–2330
Jialal I, Devaraj S, Adams-Huet B (2016) Plasma fetuin-A does not correlate with monocyte TLR4 in humans. Diabetologia 59(1):222–223
Mukhopadhyay S, Bhattacharya S (2016) Plasma fetuin-A triggers inflammatory changes in macrophages and adipocytes by acting as an adaptor protein between NEFA and TLR-4. Diabetologia 59(4):859–860
Mathews ST, Chellam N, Srinivas PR, Cintron VJ, Leon MA, Goustin AS et al (2000) Alpha2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Mol Cell Endocrinol 164(1–2):87–98
Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS et al (2002) Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 51(8):2450–2458