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Expression of liver insulin-like growth factor 1 gene and its serum level in patients with diabetes

机译:糖尿病患者肝胰岛素样生长因子1基因的表达及其血清水平

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AIM: To explore the effect of diabetic duration and blood glucose level on insulin like growth factor 1 (IGF-1) gene expression and serum IGF-1 level. METHODS: Diabetes was induced into Sprague Dawley rats by alloxan and then the rats were subdivided into different groups with varying blood glucose level and diabetic duration. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase- polymerase chain reaction (RT-PCR), IGF-1 peptide and serum IGF-1 concentration by enzyme-linked immunosorbent assay (ELISA). RESULTS: During early diabetic stage (week 2), in comparison with normal control group (NC), IGF-1 mRNA (1.17+-0.069 vs 0.79+-0.048, P<0.001; 1.17+-0.069 vs 0.53+-0.023, P<0.0005, respectively), IGF-1 peptide contents [(196.66+-14.9) ng·mg~(-1) vs (128.2+-11.25) ng·mg~(-1), P<0.0005; (196.66+-14.9) ng·mg~(-1) vs (74.43+-5.33) ng·mg~(-1), P<0.0001, respectively] were reduced in liver tissues of diabetic rats. The IGF-1 gene downregulation varied with glucose control level of the diabetic state, and deteriorated gradually further with duration of diabetes. By month 6, hepatic tissue IGF-1mRNA was 0.71+-0.024 vs 1.12+-0.056, P<0.001; 0.47+-0.021 vs 1.12+-0.056, P<0.0005, respectively. IGF-1 peptide was (114.35+-8.09) ng·mg~(-1) vs (202.05+-15.73) ng·mg~(-1), P<0.0005; (64.58+-3.89) ng·mg~(-1) vs (202.05+-15.73) ng·mg~(-1), P<0.0001 respectively. Serum IGF-1 was also lowered in diabetic group with poor control of blood glucose. On week 2, serum IGF-1 concentrations were (371.0+-12.5) ng·mg~(-1) vs (511.2+-24.7) ng·mg~(-1), P<0.0005, (223.2+-9.39) ng·mg~(-1) vs (511.2+-24.7) ng·mg~(-1), P<0.0001 respectively. By month 6, (349.6+-18.62) ng·mg~(-1) vs (520.7+-26.32) ng·mg~(-1), P<0.0005, (188.5+-17.35 vs 520.7+-26.32) ng·mg~(-1), P<0.0001, respectively. Serum IGF-1 peptide change was significantly correlated with that in liver tissue (r=0.99, P<0.001). Furthermore, No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group. CONCLUSION: The influence of diabetic status on IGF-1 gene expression in liver tissues is started from early diabetic stage, causing down regulation of IGF-1 expression, and progresses with the severity and duration of diabetic state. Accordingly serum IGF-1 level decreases. This might indicate that liver tissue IGF-1 gene expression is greatly affected in diabetes, thus contributing to reduction of serum IGF-1 level.
机译:目的:探讨糖尿病持续时间和血糖水平对胰岛素样生长因子1(IGF-1)基因表达和血清IGF-1水平的影响。方法:用四氧嘧啶将糖尿病诱导为Sprague Dawley大鼠,然后将其分为血糖水平和糖尿病持续时间不同的不同组。通过以下方法测量参数:通过逆转录酶-聚合酶链反应(RT-PCR)测量IGF-1 mRNA,通过酶联免疫吸附测定(ELISA)测量IGF-1肽和血清IGF-1浓度。结果:在糖尿病早期(第2周),与正常对照组(NC)相比,IGF-1 mRNA(1.17 + -0.069 vs 0.79 + -0.048,P <0.001; 1.17 + -0.069 vs 0.53 + -0.023,分别为P <0.0005),IGF-1肽含量[(196.66 + -14.9)ng·mg〜(-1)与(128.2 + -11.25)ng·mg〜(-1),P <0.0005;糖尿病大鼠肝组织中(196.66 + -14.9)ng·mg〜(-1)比(74.43 + -5.33)ng·mg〜(-1)降低(P <0.0001)。 IGF-1基因的下调随糖尿病状态的血糖控制水平而变化,并随着糖尿病持续时间的延长而逐渐恶化。到第6个月,肝组织IGF-1mRNA为0.71 + -0.024和1.12 + -0.056,P <0.001;分别为0.47 + -0.021和1.12 + -0.056,P <0.0005。 IGF-1肽为(114.35 + -8.09)ng·mg〜(-1)与(202.05 + -15.73)ng·mg〜(-1),P <0.0005; (64.58 + -3.89)ng·mg〜(-1)与(202.05 + -15.73)ng·mg〜(-1),P <0.0001。血糖水平控制不良的糖尿病组血清IGF-1水平也降低。第2周,血清IGF-1浓度为(371.0 + -12.5)ng·mg〜(-1)对(511.2 + -24.7)ng·mg〜(-1),P <0.0005,(223.2 + -9.39) ng·mg〜(-1)vs(511.2 + -24.7)ng·mg〜(-1),P <0.0001。到第6个月,(349.6 + -18.62)ng·mg〜(-1)对(520.7 + -26.32)ng·mg〜(-1),P <0.0005,(188.5 + -17.35对520.7 + -26.32)ng ·mg〜(-1),P <0.0001。血清IGF-1肽的变化与肝组织中的变化显着相关(r = 0.99,P <0.001)。此外,在患有血糖升高的糖尿病大鼠和非糖尿病对照组之间,上述参数没有发现差异。结论:糖尿病状态对肝脏组织IGF-1基因表达的影响始于糖尿病早期,导致IGF-1表达下调,并随糖尿病状态的严重性和持续时间而发展。因此血清IGF-1水平降低。这可能表明肝脏组织IGF-1基因表达在糖尿病中受到很大影响,从而有助于降低血清IGF-1水平。

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