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

Abstract

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.