Hyperglycemia Affects the Expression of Inflammatory Genes in Peripheral Blood Mononuclear Cells of Patients with Type 2 Diabetes

被引:23
作者
Akbari, Mohamad [1 ]
Hassan-Zadeh, Vahideh [1 ]
机构
[1] Univ Tehran, Dept Cell & Mol Biol, Fac Biol, Coll Sci, Tehran, Iran
基金
美国国家科学基金会;
关键词
Hyperglycemia; IL-1; IL-6; inflammation; Type; 2; diabetes; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-1 INDUCES INTERLEUKIN-1; INSULIN-RESISTANCE; IKK-BETA; IL-6; GLUCOSE; OBESITY; IL-1-BETA; CYTOKINE; MACROPHAGES;
D O I
10.1080/08820139.2018.1480031
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: Innate immune system dysregulation and chronic low-grade inflammation are associated with the pathogenesis of type 2 diabetes (T2D). The aim of this study was to investigate the effect of hyperglycemia on mRNA expression of four inflammatory genes in peripheral blood mononuclear cells (PBMCs) of pre-diabetic and diabetic individuals.Methods: In a case-control study, quantitative real-time PCR was used to analyze changes in IL-1, IL1R1, IL-6, and IL6ST gene expression in PBMCs of 30 T2D patients with high blood glucose levels, 24 diabetic and nondiabetic individuals with moderately high blood glucose levels and 30 controls with normal blood glucose levels.Results: In T2D patients with high blood glucose, IL-1 expression showed a 2.69-fold increase (p=0.0380), while IL-6 expression levels were 3.45 fold lower (p=0.0045) versus control subjects. Moreover, compared with control group the expression of IL1R1 and IL-6 genes both were downregulated in individuals with moderately high blood glucose levels by 2.38 (p=0.0365) and 4.34 fold (p=0.0027), respectively. In addition, hemoglobin A1C (A1C) levels were positively correlated with IL-1 expression and fasting plasma glucose (FPG) levels showed a positive correlation with IL-1 and a negative correlation with IL-6 expression.Conclusion: The observed changes in both IL-1 and IL-6 mRNA levels in PBMCs may contribute to the development of inflammatory processes involved in the pathogenesis of T2D. Downregulation of IL1R1 in individuals with mild hyperglycemia may indicate an attempt to reduce the pro-inflammatory effects of IL-1 via auto-stimulation.
引用
收藏
页码:654 / 665
页数:12
相关论文
共 41 条
[1]   IL-6 signalling pathways and the development of type 2 diabetes [J].
Akbari, Mohamad ;
Hassan-Zadeh, Vahideh .
INFLAMMOPHARMACOLOGY, 2018, 26 (03) :685-698
[2]   IKK-β links inflammation to obesity-induced insulin resistance [J].
Arkan, MC ;
Hevener, AL ;
Greten, FR ;
Maeda, S ;
Li, ZW ;
Long, JM ;
Wynshaw-Boris, A ;
Poli, G ;
Olefsky, J ;
Karin, M .
NATURE MEDICINE, 2005, 11 (02) :191-198
[3]   Increased interleukin (IL)-1β messenger ribonucleic acid expression in β-cells of individuals with type 2 diabetes and regulation of IL-1β in human islets by glucose and autostimulation [J].
Boni-Schnetzler, Marianne ;
Thorne, Jeffrey ;
Parnaud, Geraldine ;
Marselli, Lorella ;
Ehses, Jan A. ;
Kerr-Conte, Julie ;
Pattou, Francois ;
Halban, Philippe A. ;
Weir, Gordon C. ;
Donath, Marc Y. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (10) :4065-4074
[4]   Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB [J].
Cai, DS ;
Yuan, MS ;
Frantz, DF ;
Melendez, PA ;
Hansen, L ;
Lee, J ;
Shoelson, SE .
NATURE MEDICINE, 2005, 11 (02) :183-190
[5]   Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase [J].
Carey, Andrew L. ;
Steinberg, Gregory R. ;
Macaulay, S. Lance ;
Thomas, Walter G. ;
Holmes, Anna G. ;
Ramm, Georg ;
Prelovsek, Oja ;
Hohnen-Behrens, Cordula ;
Watt, Matthew J. ;
James, David E. ;
Kemp, Bruce E. ;
Pedersen, Bente K. ;
Febbraio, Mark A. .
DIABETES, 2006, 55 (10) :2688-2697
[6]   INTERLEUKIN-1 INDUCES INTERLEUKIN-1-ALPHA AND INTERLEUKIN-1-BETA GENE-EXPRESSION IN SYNOVIAL FIBROBLASTS AND PERIPHERAL-BLOOD MONOCYTES [J].
DALTON, BJ ;
CONNOR, JR ;
JOHNSON, WJ .
ARTHRITIS AND RHEUMATISM, 1989, 32 (03) :279-287
[7]   High glucose induces IL-1β expression in human monocytes:: mechanistic insights [J].
Dasu, Mohan R. ;
Devaraj, Sridevi ;
Jialal, Ishwarlal .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2007, 293 (01) :E337-E346
[8]   Type 2 diabetes as an inflammatory disease [J].
Donath, Marc Y. ;
Shoelson, Steven E. .
NATURE REVIEWS IMMUNOLOGY, 2011, 11 (02) :98-107
[9]   Hyperglycemia-induced β-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes [J].
Donath, MY ;
Gross, DJ ;
Cerasi, E ;
Kaiser, N .
DIABETES, 1999, 48 (04) :738-744
[10]   Increased number of islet-associated macrophages in type 2 diabetes [J].
Ehses, Jan A. ;
Perren, Aurel ;
Eppler, Elisabeth ;
Ribaux, Pascale ;
Pospisilik, John A. ;
Maor-Cahn, Ranit ;
Gueripel, Xavier ;
Ellingsgaard, Helga ;
Schneider, Marten K. J. ;
Biollaz, Gregoire ;
Fontana, Adriano ;
Reinecke, Manfred ;
Homo-Delarche, Francoise ;
Donath, Marc Y. .
DIABETES, 2007, 56 (09) :2356-2370