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The Effect of Insulin Postreceptor Signal Pathway in Pathogenesis of Gestational Diabetes Mellitus

Author: HeMing
Tutor: ZouLi
School: Huazhong University of Science and Technology
Course: Obstetrics and Gynaecology
Keywords: Gestational Insulin Resistance Glucose transporter protein-4 Gestational Protein kinase B Phosphatidylinositol 3 - kinase Glycogen synthase kinase-3 Sodium vanadate The insulin receptor substrate-1
CLC: R714.2
Type: PhD thesis
Year: 2009
Downloads: 344
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Abstract


GLUT-4 expression and translocation change analysis in the first part of the GLUT-4 expression and translocation GDM insulin resistance relations purpose of GDM in skeletal muscle GLUT-4 expression and translocation change GDM abnormal glucose metabolism and The relationship between insulin resistance. Methods 26 cases of patients with GDM (GDM group) and normal glucose tolerance pregnant women over the same period 26 patients (control group), fasting blood were collected and extracted complete rectus abdominis tissue samples. (1) by radioimmunoassay and glucose oxidase test groups fasting insulin (FINS) and fasting plasma glucose (FPG) levels; application homeostasis model insulin resistance index (HOMA-IR); (2) using RT-PCR method and western blot assay in skeletal muscle GLUT-4 expression and translocation change; (3) immunohistochemical assay GLUT-4 distribution in the muscle tissue. Results (1) GDM group FPG, FINS, HOMA-IR water on average significantly higher than that of the control group, all indicators were compared, the differences were statistically significant (P <0.05); (2) GDM group and the control group between the bones there is no significant difference (P> 0.05); muscle GLUT-4 total (3) GDM group from skeletal muscle intracellular membrane translocation to the outer membrane of the number of GLUT-4 significantly reduced compared with the control group (P <0.05), the correlation analysis display the number of GLUT-4 translocation with FPG, FINS, HOMA-IR index was negatively correlated (r = -0.42, -0.46, -0.51, P <0.05). Appear in the conclusion of GDM in skeletal muscle GLUT-4 translocation abnormalities, may be one of the molecular mechanisms cause GDM glucose uptake the obstacles and insulin resistance. In the second part of the GDM skeletal muscle tissue PI3-K, PKB and GSK-3β expression and activity change the purpose of insulin receptor key molecule in the signal transduction process PI3Kp85 PKB, GSK-3β in skeletal muscle tissue of patients with GDM expression and activity changes. Methods 26 cases of patients with GDM (GDM group) over the same period with normal glucose tolerance pregnant women, 26 cases (control group), to extract the full the rectus abdominis live tissue samples. (1) using immunohistochemical methods to detect PI3Kp85, PKB, GSK-3β expression; (2) application of the Western blot assay GDM skeletal muscle PKB, GSK-3β protein phosphorylation situation; (3) ELISA assay muscle tissue PI3 -K activity. Results (1) signal transduction molecules in the GDM group PKB and GSK-3β protein expression was not found in a number of different (P> 0.05); the protein of PI3Kp85 (2) GDM group compared with the control group compared with the control group high level (P <0.05); (3) GDM group PKB, GSK-3β phosphorylation level and activity of PI3-K significantly lower than the control group, the difference was significant (P <0.05). Conclusions in GDM skeletal muscle insulin receptor signaling protein expression was no significant change in the GDM group and the control group, but there PI3-K and of PKB and GSK-3β activity down, is a cause the GDM of insulin resistance and GLUT-4's The indexable decline receptor reasons. The third part of sodium vanadate GDM insulin receptor signaling pathway regulation of IRS-1 tyrosine phosphorylation of IRS-1 tyrosine phosphorylation Objective To study the tyrosine phosphorylation accelerator sodium vanadate regulation of GDM skeletal muscle in insulin signal transduction pathway of PI-3K of PKB activity and GLUT-4 translocation, and to explore the promotion of IRS-1 tyrosine phosphorylation GDM insulin receptor signaling. Methods 26 cases of patients with GDM (GDM group), 26 cases of pregnant women of the same period with normal glucose tolerance (control group), to extract a complete skeletal muscle tissue samples after incubation with sodium vanadate, sucrose gradient centrifugation cell outer membrane extract total protein . (1) Application immunoprecipitation detection of IRS-1 tyrosine phosphorylation levels; (2) ELISA assay PI3-K activity in muscle tissue; (3) and Western blot detection of GDM skeletal muscle PKB phosphorylation and skeletal muscle organizational changes in GLUT-4 translocation. Results (1) sodium vanadate role of in GDM skeletal muscle tissue, IRS-1 tyrosine phosphorylation mediated PI3-k activity was significantly increased, the difference was statistically significant (p <0.05); (2) sodium vanadate The role of skeletal muscle GLUT-4 the transmembrane translocation also increased significantly; (3) but their level is still lower than that of the control group (p <0.05) after sodium vanadate effect. GDM Conclusion improve the tyrosine phosphorylation of IRS-1, can increase the activity of PI3-K and GLUT-4 translocation, part of the improvement GDM insulin signaling, promote IRS-1 tyrosine phosphorylation may be the treatment of insulin resistance potential targets.

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CLC: > Medicine, health > Obstetrics and Gynaecology > Obstetrics > Pathological pregnancy ( abnormal pregnancy )
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