Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption,...Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.展开更多
INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced b...INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).展开更多
Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by allox...Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P <0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P <0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P <0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P <0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ~ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ~(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P <0. 001; amplitude ofevokedpotential: r = 0. 716, P <0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P < 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.展开更多
基金Changshu Science and Technology Plan(Social Development)Project(No.CS202130)Key Project of Changshu No.2 People’s Hospital(No.CSEY2021007)。
文摘Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.
基金the National Natural Science Foundation of China,No.39260033.
文摘INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).
基金This work was supported by the National Natural Sciences Foun-dation of China.This work was originally published in Chinese Journal of Internal Medicine (2001 40(2): 93-7)in Chinese.
文摘Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P <0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P <0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P <0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P <0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ~ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ~(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P <0. 001; amplitude ofevokedpotential: r = 0. 716, P <0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P < 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.