| It shows an increasing tendency year by year in diabetes mellitus that has severe harm to people's heath, and Type 2 accounts for more than 90% of diabetes mellitus. Type 2 diabetes mellitus (DM2) is a metabolic syndrome characterized by insulin resistance and lack of insulin secretion. Heredity and environment are two factors to DM2 pathogenesis. However, ethanol, as an important risk factor to DM2, has been extensive studied mainly for its damage to pancreatic isletβ-cell resulting in insufficient insulin secretion. In other aspects, particularly insulin resistance in target tissues of insulin is not yet researched in depth.It shows a increasing tendency year by year in diabetes mellitus that has severe harm to people's heath, and Type 2 accounts for more than 90% of diabetes mellitus. Type 2 diabetes mellitus(DM2) is a metabolic syndrome characterized by insulin resistance and lack of insulin secretion. Heredity and environment are two factors to DM2 pathogenesis. However, ethanol, as an important risk factor to DM2, has been extensive studied mainly for its damage to pancreatic isletβ-cell resulting in insufficient insulin secretion. In other aspects, particularly insulin resistance in target tissues of insulin is not yet in-depth researched.Glucocorticoids have been documented as physiological functional antagonists of insulin action. They can result in insulin resistance within target tissues through impairing insulin-dependent glucose uptake, increasing lipolysis and improving hepatic gluconeogenesis. 11β-Hydroxysteroid dehydrogenase Type 1(11β-HSD1), which is one key enzyme in the local tissues as a regulator of glucocorticoid activity, can catalyze the conversion of inert 11-keto glucocorticoids (cortisol, corticosterone) into active forms (cortisone, 11-dehydrocorticosterone) in whole organs and active glucocorticoids can oppose insulin physiological functions with ?binding to glucocorticoids receptors (GR). However, there is no report on the role of 11β-HSD1 and GR in DM2 induced by ethanol.As the biggest organ of metabolism, Liver plays a central role in glycometabolism, lipometabolism and protein metabolism, in addition, it is a key organ suffering from insulin resistance. In physio-states, insulin regulates key enzymes of glycometabolism in hepatocytes to limit gluconeogenesis and enhance lipolysis through insulin signaling pathway. It has been reported that there are some abnormal expressions of the key enzymes associated with enhancement of activity of glucocorticoids in liver insulin resistance. Therefore, it is essential to investigate deeply the expression and effect to the key enzymes in glycometabolism of 11β-HSD1.Objective:To supply evidence and animal experimental base to prevention and treatment of type 2 diabetes mellitus (DM2) induced by excessive alcohol consumption throuh revealing that the effect of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and glucocorticoid receptors (GR) in type 2 diabetes mellitus (DM2) induced by high dose of ethanol.Methods:Wistar rats were divided into Control group and Ethanol group. Ethanol group were given intragastric administration of 36% concentration alcohol (4g kg-1d-1) while Control group were instead of water. The whole term lasted three months. Glucose tolerance test, insulin tolerance test and relevant index calculation were used to evaluate the fasting blood glucose, self-regulating ability of blood glucose and levels of insulin sensitivity and insulin resistance for analysis of analogues. On the successful analogues, the expression levels in liver of 11β-HSD1 and GR, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase), which are two rate-limiting enzymes in gluconeogenesis, as well as glycogen synthase kinase-3 (GSK-3), were assessed in two groups by Western Blot.Results:1. The body weights of rats from Ethanol group grew stably with ages and the increase was not abnormal compared with Conrol group;2. At the end of the first and second month, there was no abnormality in fasting blood glucose and self-regulating ability of blood glucose of rats from Ethanol group. At the end of the third month, fasting blood glucose of the rats from Ethanol group increased remarkably compared with those from Conrol group (p<0.01) and the rats from Ethanol group had abnormal regulating ability of blood glucose;3. Fasting insulin of the rats from Ethanol group was impaired (p<0.05) and whole body insulin resistance has happened (ITT 2h glucose, p<0.05),4. Insulin sensitivity index(ISI), insulin secretion index(IS) and HβCI were all decreased in the rats from Ethanol group;5. 11β-HSD1 and GR protein expression in liver were both significantly increased in alcohol intake rats (P<0.05);6. The rats of ethanol group showed an increasing expression of the rate-limiting enzymes of , PEPCK and G-6-Pase (P<0.05);There was a significantly increase of GSK-3αin liver from ethanol group (P<0.05);Conclusion:1. Long-term excessive alcohol consumption in rats can cause increasing fasting blood glucose, IGT, impaired insulin secretion function and insulin resistance, which are characteristics of Type 2 diabetes mellitus;2. After a long-term excessive ethanol intake, the protein expression of 11β-HSD1 and GR in liver increased significantly as well as PEPCK, G-6-Pase and GSK-3α;3. The mechanism of Type 2 diabetes mellitus induced by high dose of ethanol may be the abnormal expression of some key enzymes in gluconeogenesis and glycogen synthesis affected by GR mediated by 11β-HSD1.
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