Li Jian-Bo, Wang Cheng-Ya, Chen Jia-Wei, Feng Zhen-Qing, Ma Hong-Tai
Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
World J Gastroenterol. 2004 Jan 15;10(2):255-9. doi: 10.3748/wjg.v10.i2.255.
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.
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).
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.
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.
探讨糖尿病病程和血糖水平对胰岛素样生长因子1（IGF-1）基因表达及血清IGF-1水平的影响。
用四氧嘧啶诱导斯普拉格-道利大鼠患糖尿病，然后将大鼠按血糖水平和糖尿病病程分成不同组。测量参数如下：用逆转录聚合酶链反应（RT-PCR）检测IGF-1 mRNA，用酶联免疫吸附测定（ELISA）检测IGF-1肽和血清IGF-1浓度。
在糖尿病早期（第2周），与正常对照组（NC）相比，糖尿病大鼠肝组织中IGF-1 mRNA（分别为1.17±0.069对0.79±0.048，P<0.001；1.17±0.069对0.53±0.023，P<0.0005）、IGF-1肽含量[分别为(196.66±14.9) ng/mg(-1)对(128.2±11.25) ng/mg(-1)，P<0.0005；(196.66±14.9) ng/mg(-1)对(74.43±5.33) ng/mg(-1)，P<0.0001]降低。IGF-1基因下调随糖尿病状态的血糖控制水平而变化，并随糖尿病病程进一步逐渐恶化。到第6个月时，肝组织IGF-1mRNA分别为0.71±0.024对1.12±0.056，P<0.001；0.47±0.021对1.12±0.056，P<0.0005。IGF-1肽分别为(114.35±8.09) ng/mg(-1)对(202.05±15.73) ng/mg(-1)，P<0.0005；(64.58±3.89) ng/mg(-1)对(202.05±15.73) ng/mg(-1)，P<0.0001。血糖控制差的糖尿病组血清IGF-1也降低。在第2周时，血清IGF-1浓度分别为(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)对(511.2±24.7) ng/mg(-1)，P<0.0001。到第6个月时，分别为(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肽变化与肝组织变化显著相关（r=0.99，P<0.001）。此外，血糖正常的糖尿病大鼠与非糖尿病对照组在上述参数上无差异。
糖尿病状态对肝组织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程度和病程进展。相应地血清IGF-1水平降低。这可能表明糖尿病时肝组织IGF-1基因表达受到很大影响，从而导致血清IGF-1水平降低。
