| Background and ObjectivesIn the clinical setting, the vast majority of patients with diabetes have blood lipid disorder, but its mechanism is not yet clear. Recent studies showed that insulin-induced gene (INSIG)-sterol regulatory element binding protein cleavage activating protein (SCAP)-sterol regulatory element binding protein (SREBP) pathway played an important role in the balance of the maintenance of intracellular cholesterol and fatty acids, and the1,25-(OH)2D3/LCA acting elements in the INSIG-2promoter region had a direct act on the vitamin D receptor (VDR)-mediated transcription of INSIG-2mRNA in vivo. Insulin can inhibit the activity of the INSIG-2gene expression in liver, thereby stimulating the transport of SREBP-lc/SCAP complex from the endoplasmic reticulum to the Golgi; Insulin strongly induces INSIG-1expression by SREBP-1c. Recombinant human insulin and insulin analogues in clinical practice are widely used, in addition to the hypoglycemic effect, the molecular biology research in the past mainly concentrated on its cancerogenic security, while the regulatory mechanism of recombinant human insulin and insulin analogues and whether there are different effects in the lipid metabolism is unknown. This study aimed to explore the influence of different insulin on the expression of1NSIG-1mRNA,1NSIG-2mRNA, VDR mRNA and SREBP-1c mRNA and whether there was difference in the liver cells in vitro experiments at the molecular level. And then explored the possible mechanism of insulin regulation of lipid metabolism, as well as the possible relationship of the various lipid metabolism-related genes.Materials and MethodsThis study used RT-PCR technique to observe the expression of INSIG-1mRNA, INSIG-2mRNA, VDR mRNA and SREBP-1c mRNA in the medium which contained different concentration of recombinant human insulin or insulin analogues interfered BRL rat liver cells cultured in a different period of time.Results1. Under the interference of recombinant human insulin and a variety of insulin analogues, the expression of INSIG-2mRNA and VDR mRNA in BRL rat liver cells was decreased (P<0.05), and the expression of both changed uniformly;2. Compared with other insulin, the downward effect of INSIG-2mRNA and VDR mRNA of Detemir was more obvious(P<0.01);3. Compared with the normal control group, all types of insulin could raise the expression of INSIG-1mRNA and SREBP-1c mRNA in BRL rat liver cells (P<0.05)4. Compared with other insulin, the upward effect of INSIG-1mRNA and SREBP-1c mRNA of Detemir was more obvious(P<0.01).Conclusions1. Different insulin can decrease the expression of INSIG-2mRNA and VDR mRNA, and raise the expression of INSIG-1mRNA and SREBP-1c mRNA in BRL rat liver cells to reach the balance of the lipid;2. Different insulin has diffferent influence on the gene expression of INSIG-1, INSIG-2, VDR, and SREBP-1c, and compares with other insulin, the downward effect of INSIG-2mRNA and VDR mRNA and the upward effect of INSIG-1mRNA and SREBP-1c mRNA of Detemir are more obvious;3. Detemir has a more significant downward effect on INSIG-2mRNA in rat liver cells compares with other insulin, which consists with the previous studies results of3T3一L1cells had the relative downward effect on INSIG-2mRNA. |
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