The Effect Of Chronic Alcohol Intake On The Insulin Sensitivity Of Adipose Tissue In Male Rats

Our country has a large consumption of ethanol. Many epidemiological researches have showed that: drinking is one of the risk factors of diabetes mellitus, especially type 2 diabetes mellitus. In the latest 10 years, with the development of economy and life standard, the prevalence of diabetes mellitus in our country has becoming the main public health problem. Insulin resistance (IR) is one of the important mechanisms in the development of type 2 diabetes mellitus and insulin signal transduction pathway plays a key role in this course. Adipose tissue is one of the main target organs of insulin. Cytokines it excretes such as TNF-αand leptin play an important even leading role in the development of IR. The prophase experiments in our laboratory have indicated that acute and chronic ethanol intake inhibit the mRNA expression of IRS-1, the key molecular of the insulin signal transport pathway. But there were no complete analysis of the whole signal transport pathway, and has not done special study on each target organ. In present study, we use the male Wistar rat in order to study to study the effect of chronic ethanol intake on the insulin sensitivity in the adipose tissue, as well as discussing the mechanism of long period chronic ethanol intakes influence on insulin sensitivity by studying the key signal molecular InsR,IRS1,PI3-K,Glut4 mRNA expression level, providing reference for the further study of the mechanism of the effect of long-time alcohol intake on insulin sensitivity. Study the TNF-α, Leptin concentration in the blood serum and mRNA expression changes in the adipose tissue at the same time which will offer us different clues for the study of ethanol's effect on the insulin resistance.Contents of Investigation: In present study, ethanol, at the dose of 0,10%,20%, 33%(v/v,10ml/kg.bw.d), was given by means of intragastric gavage to male Wistar rats. The control group and low, medium, high dosage groups were set up. After eighteen weeks, we have the oral glucose tolerance test (OGTT). Nineteen weeks later, rats were killed and serum was collected for testing of fasting glucose, insulin, TNF-αand leptin concentration. HOMA(Homeostasis Model Assessment) (HOMA-IR=[FPG(mmol/L)×FIN(mIU/L)]/22.5 ) and HOMAβ-cell index, (HBCI=20×FINS/(FPG-3.5)) of each group were calculated, based on the fasting glucose and insulin, to indicate insulin sensitivity and insulin secretion function. The adipose tissue of the rats were Separated and the total RNA were extracted for testing the mRNA expression of the InsR,IRS1,PI3-K,Glut4,TNF-α,Leptin in the adipose tissue by RT-PCR method.Results:1. Effect of chronic ethanol intake on the concentration of serum glucose and insulin: with the dosage of ethanol intake increase, the serum glucose concentration increases gradually, and the serum glucose concentration in the high dosage group was the highest. Serum insulin concentration increases gradually too, and the highest concentration occurs in the medium group. The HOMA-IR increases in every ethanol dosage groups, with the medium dosage group having the highest HOMA-IR, the HBCI decreases in the highest dosage group.2. Effect of chronic ethanol intake on the mRNA expression of InsR,IRS1,PI3-K,Glut4 in the adipose tissue of rats: The mRNA expression of InsR,IRS1,Glut4 were increased with the increasing of the ethanol dosage and the medium dosage group has the highest expression; Compared with the control group, the expression level of PI3-K mRNA has increasing trend too, but the difference is not significant, the low dosage group has the highest expression level.3. Effects of chronic ethanol intake on the serum concentration of TNF-α,Leptin and the mRNA expression of TNF-α,Leptin in the adipose tissue: The serum concentration of TNF-αin the alcohol groups all increased and the low dosage group has the highest concentration. The serum concentration of Leptin in the alcohol groups decreased and the medium dosage group has the lowest concentration. The mRNA expression of TNF-α,Leptin were all increased in the alcohol groups. The medium dosage group has the highest expression level of TNF-αand the low dosage group has the highest expression level of Leptin.Conclusions:1. Chronic ethanol intake can cause insulin resistance and damage the secretion function ofβ-cell, forming high serum glucose and high serum insulin syndrome and so on.2. Chronic ethanol intake can induce the expression of key molecular in the insulin signal transduction pathway compensatory increase. These indicate rats are insulin resistance so need more key molecular transform insulin signal.3. Chronic ethanol intake can increase the serum concentration of TNF-αand attribute to the decreasing trend of leptin, indicating TNF-α,leptin may attribute to the insulin resistance. The expression level of TNF-αand leptin were all increase which may be the mechanism of the action of TNF-α,leptin in the insulin resistance reduced by chronic ethanol intake.