Effects of myeloid-derived growth factor on insulin resistance and inflammatory response of liver from type 2 diabetic mice
SU Fang1, FU Zhiguang1, FANG Wencan2, WANG Ying2, HE Mingjuan3, ZHANG Yongbin4
1. Department of Aeromedical Physiological Identification and Training, Characteristics Medical Center of PLA Air Force, Beijing 100142, China; 2. PLA Medical School, Beijing 100853, China; 3. Department of Endocrinology, the Fourth Hospital Wuhan, Wuhan 430033, China; 4. Department of Otolarynology, Beijing Hospital of Nuclear Industry, Beijing 100045, China
Abstract：Objective To investigate the effects of myeloid-derived growth factor (MYDGF) on insulin resistance and inflammatory response of liver from type 2 diabetic mice. Methods C57 mice were randomly divided into Vehicle group, DM group and MYDGF group. After administration for 12 weeks, fasting blood glucose (FBG), insulin and HOMA-IR were determined. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Catalase in the liver were measured. Morphological changes of liver were assessed by HE staining. Phosphorylation levels of IKKβ and IkBα were detected by Western blot. Results Compared with DM group, the levels of FBG[(6.91±0.71) mmol/L vs. (19.46±1.12) mmol/L], and insulin in MYDGF group[(13.29±1.42) Mu/L vs. (21.88±1.58) Mu/L] and HOMA-IR[(4.08±0.65) vs. (18.90±1.37)] obviously decreased (P<0.05). The concentrations of TNF-α[(32.17±3.18)ng/L vs. (66.39±4.51) ng/L] and IL-6 [(13.65±0.89) ng/L vs. (21.55±3.27) ng/L] also significantly decreased (P<0.05). Liver SOD [(297.54±20.43) U/mg vs. (198.32±19.29) U/mg], GSH-Px[(0.65±0.05) U/mg vs. (0.19±0.04) U/mg] and Catalase [(220.34±19.82) U/mg vs. (134.69±18.81) U/mg] levels increased (P<0.05); in addition, inflammatory cell infiltration and hepatocyte steatosis attenuated; lastly, phosphorylation levels of IKKβ [p-IKKβ:IKKβ, (0.97±0.10) vs. (1.39±0.11)] and IkBα [p-IκBα:IκBα, (0.93±0.07) vs. (1.44±0.06)] significantly increased (P＜0.05) in MYDGF group. Conclusions MYDGF improves insulin resistance, which may be attributed to attenuated inflammatory response from diabetic liver via activating the IKKβ/IkBα signaling pathway.
苏芳, 付之光, 方文灿, 王莹, 贺明娟, 张永彬. 髓源性生长因子对2型糖尿病小鼠胰岛素抵抗及肝脏炎性反应的影响[J]. 武警医学, 2024, 35(3): 201-204.
SU Fang, FU Zhiguang, FANG Wencan, WANG Ying, HE Mingjuan, ZHANG Yongbin. Effects of myeloid-derived growth factor on insulin resistance and inflammatory response of liver from type 2 diabetic mice. Med. J. Chin. Peop. Armed Poli. Forc., 2024, 35(3): 201-204.
Lassailly G, Caiazzo R, Pattou F, et al. Perspectives on treatment for nonalcoholic steatohepatitis[J]. Gastroenterology, 2016,150(8):1835-1848.
[4]
Korf-Klingebiel M, Reboll M R, Klede S, et al. Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction[J]. Nat Med, 2015,21(2):140-149.
[5]
Wang L, Li Y, Guo B, et al. Myeloid-derived growth factor promotes intestinal glucagon-like peptide-1 production in male mice with type 2 diabetes[J]. Endocrinology, 2020,161(2):bqaa003.
van der Windt D J, Sud V, Zhang H, et al. Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis[J]. Hepatology, 2018,68(4):1347-1360.
[11]
Baeck C, Wehr A, Karlmark K R, et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury[J]. Gut, 2012,61(3):416-426.
[12]
Cai Y, Li H, Liu M, et al. Disruption of adenosine 2A receptor exacerbates NAFLD through increasing inflammatory responses and SREBP1c activity[J]. Hepatology, 2018,68(1):48-61.
[13]
Ben-Shlomo S, Zvibel I, Shnell M, et al. Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase[J]. J Hepatol, 2011,54(6):1214-1223.
[14]
Liu Z, Mar K B, Hanners N W, et al. A NIK-SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB[J]. Nature, 2019,568(7751):249-253.
Mokgalaboni K, Ntamo Y, Ziqubu K, et al. Curcumin supplementation improves biomarkers of oxidative stress and inflammation in conditions of obesity, type 2 diabetes and NAFLD: updating the status of clinical evidence[J]. Food Funct, 2021,12(24):12235-12249.
[17]
Li J, Wang T, Liu P, et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD[J]. Food Funct, 2021,12(9):3898-3918.
[18]
Farzanegi P, Dana A, Ebrahimpoor Z, et al. Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation[J]. Eur J Sport Sci, 2019,19(7):994-1003.
[19]
Wronka M, Krzemińska J, Młynarska E, et al. The influence of lifestyle and treatment on oxidative stress and inflammation in diabetes[J]. Int J Mol Sci, 2022,23(24):15743.
2024, Vol. 35 
