Dissertation > Excellent graduate degree dissertation topics show

The Giucose-lowering Effect of Stilbenoids E2 and Its Mechanism

Author: ChenJinLong
Tutor: WuZuZe
School: PLA Military Academy of Medical Sciences
Course: Pathology and Pathophysiology
Keywords: Stilbene compounds E2 Diabetes Insulin receptor Sphingosine kinase Glucose metabolism
CLC: R96
Type: PhD thesis
Year: 2007
Downloads: 289
Quote: 1
Read: Download Dissertation


Diabetes is characterized by hyperglycemia, which results from impaired insulin secretion and/or insulin action. It is also the leading cause of many clinical chronic complications, which lead to a markedly increased morbidity and mortality. Drugs currently used in clinical practices could not correct the abnormality of diabetes with satisfaction. Therefore, it is still an important mission in the world to find a more effective agent in the treatment and prophylaxis of diabetes.Stilbenoids E2, a derivate from rheum officinal rootstock, is a kind of glucose-lowering agent owned by our laboratory. However, we know little about its glucose-lowering mechanism and complication improving effects. In order to evaluate its glucose-lowering effects and clarify the underlying mechanisms, we performed a systemic research using several experimental diabetic animal models.. Meantime, we investigated the role of SPK in the regulation of glucose metabolism, and tested the possibility of taking it as a new target in managing the diabetes mellitus..First, we observed the functions of Stilbenoids E2 on glucose-lowering and complication controlling by using 5 kind experimental animal models The results showed that Stilbenoids E2 could decrease the serum glucose, triglyceride and cholesterol levels, and could markedly improve the oral glucose tolerance of the diabetic animals. Stilbenoids E2 could not promote the secretion of insulin but protect the islet cells. Stilbenoids E2 showed a potent ability to protect and reconstruct many organs, such as the heart, kidney, liver and spleen. Glucogen synthesis in the rat liver and heart was accelerated after the administration of Stilbenoids E2. Stilbenoids E2 could also improve the rat’s heart output through the decomposing glycosylating terminal products-AGEs, decreasing the distal resistance of blood vessels, and improving the compliances of the arteries. Western Blot results showed that stilbenoids E2 could increase the expression of insulin receptor in the liver and activate the signaling pathways of Akt、GSK-3βin the liver and heart tissues. we then probed the molecular and cellular mechanisms of stilbenoids E2 for its abilities to decrease the serum levels of triglyceride and cholesterol, and its controlling on the related complications. Stilbenoids E2 enhanced the consumption of hepatin in the L0-2 liver cells but not in the C2C12 muscle cells, impling that the liver cells might be a target of stilbenoids E2. We found that stilbenoids E2 could not induce insulin secretion of theβTC3 islet cells, but could active the phosphorylation of Akt and GSK-3βin the SMMC-7721 hepatoma cells. We also found that stilbenoids E2 could activate the SPK, another important lipid kinase as PI3K. To clarify whether SPK is really a key molecule involved in the glucose metabolism, we prepared the Ad-SPK1, the recombinant adenovirus harboring SPK1 gene, then transfected the SMMC-7721 hepatoma cells and C2C12 myoblasts with Ad-SPK1. We found that SPK1 gene tranfer could significantly increase both basal and insulin-induced glucose uptake, and DMS, a potent inhibitor of SPK1, inhibited both basal and insulin-induced glucose uptake. We further investigated the role of SPK1 in glucose metabolism in the spontaneous KK-Ay type 2 diabetic mice model using a adenoviral-mediated gene transfer approach. It was found that the adenoviral-mediated gene transfer of SPK1 markedly decreased blood glucose levels and alleviated their insulin-resistance of the animals. All these findings strongly suggest that SPK1 is a key molecule in modulating the glucose metabolism, and stimulating activation of SPK may be an important mechanism of the anti-diabetic action of stilbenoids E2.In conclusion, our results demonstrate that: (1) Stilbenoids E2 can decrease the blood glucose and lipid levels, improve the structures and functions of the heart, liver, spleen and kidney, so it is a new and effective agent in the treatment of diabete. (2) The glucose-lowering mechanism of Stilbenoids E2 are:①Protect the islet cells but do not stimulate the secretion of insulin;②Increase the expression of insulin receptors;③Accelerate the glycogen synthesis in the liver and the heart through activating Akt and GSK-3βsignaling;④stimulating activation of SPK is an important mechanism of the anti-diabetic action of stilbenoids E2. (3) SPK is a another lipid kinase involved in the regulation of glucose metabolism and homeostasis.

Related Dissertations

  1. Serum A-FABP Levels and Its Expression in Atherosclerotic Plaques of Diabetes Mellitus,R587.1
  2. Professor Liu Yanchi academic thought and clinical experience and clinical studies for treatment of diabetes,R249
  3. Common TCM syndrome and serum homocysteine ??and diastolic function relationships of the newly diagnosed patients with type 2 diabetes,R259
  4. The Effect and Pharmacological Analysis of Houttuynia Cordata Thunb (HCT) on Diabetes Mellitus,R285.5
  5. Effect of High Glucose on Chemokine Ligand 16 (CXCL16) Expression and Secretion in THP-1 Macrophages and Intervention of Aspirin in the Activity,R587.2
  6. The Effect and Mechanism of p38MAPK Inhibitor CBS3830 on Intimal Hyperplasia in Autogenous Vein Grafts of Diabetic Rats,R587.1
  7. Effect of β-Casomorphin7 or Casein Peptides on Blood Glucose and Oxidative Stress of the Diabetic Rats,R587.1
  8. Experimental Study of Influence of Atrovastatin on Expression of NF-κB in Retionpathy of Diabetic Rats,R587.1
  9. Relationship between Level of Serum Uric Acid and Lower Extremity Arterial Disease in Patients with Type 2 Diabetes Mellitus,R587.1
  10. Improvement of Interleukin Profiles in Patients with Type 2 Diabetes Mellitus After Add-on Acarbose Therapy Independent of Glycemic Control,R587.1
  11. Efficacy and Safety of Biphasic Insulin Aspart 30 Once-daily Treatment in Patients with Type 2 Diabetes,R587.1
  12. The Blood Glucose Control and Influencing Factors in Type 2 Diabetic Patients with Oral Hypoglycemic Agents,R587.1
  13. The Analysis of Related Factors in Type 2 Diabetes with Depression,R587.1
  14. Effect of β-Casomorphin-5 on Blood Glucose and Oxidative Stress of Diabetic Rats,R587.1
  15. Study on the Protein Composition of Intestinal Flora in the Antibiotics Interfered Mice and the Bacteria-related Diseases,R446.5
  16. The Effects of Aerobic Exercise Training on Oxidative Stress and Ultrastructure of Pancreatic Organization in Diabetic Rats,R587.1
  17. Study on Type 2 Diabetes Associated with the Northwest Dryness Syndrome and Intervention Therapy,R259
  18. Carotid Artery Wall Elasticity and Carotid Atherosclerosis in Diabetes Mellitus Patients with Microalbuminuria Using Ultrasonographic Elastography and High-freguency Ultrasound,R445.1
  19. Correlation Analysis between Coronary Lesion Severity and Peripheral Blood Cell CD34~+ Ratio in the Coronary Heart Disease Patients Complicating Diabetes Mellitus,R541.4
  20. Association of Genetic Variation of UTS2 Gene with Type2 Diabetes Mellitus and Hypertension,R587.1
  21. The Espression of C-reactive Protein in Rats of the Chronic Obstructive Pulmonary Disease with Diabetic,R563.9

CLC: > Medicine, health > Pharmacy > Pharmacology
© 2012 www.DissertationTopic.Net  Mobile