| Low doses or moderate drinking of alcohol is associated with decreased risk of type 2 diabetes, whereas excessive heavy dose alcohol consumption is an independent risk factor for type 2 diabetes, and the exact mechanism by which alcohol contributes to the risk is still unclear. Long-term excessive alcohol consumption can cause majority of organ diseases in human bodies. Some studies have confirmed that alcohol consumption cause injury on the islet itself, but the role and mechanism that how injury is emerged is not thoroughly understood. Our preliminary works show that substantial long-term alcohol intake of pregnant offspring had whole body insulin resistance. This study at the preparatory work on the basis of substantial long-term alcohol consumption can increase the adult rat diabetes risk, as well as conduct a study to explore its mechanism. For protection from diabetes and provide guidance to people rational use of alcohol, we study of the effect of long-term and heavy doses alcohol consumption on blood glucose regulation function in rats and the mechanism that how did it happen and also provide a successful animal model of IGT to the follow-up study on the mechanism of insulin resistance.Objective:Study on the effects of substantial long-term alcohol drinking on glucose metabolism and islet function in wistar rats, to explore possible mechanisms that alcohol drinking cause damage to the islet. Try to explain the relationship between long-term excessive alcohol consumption and diabetes from the perspective of islet destruction on substantial.Methods:Wistar rats were divided into Control group and Ethanol group. Ethanol group were intragastric administration by 36% concentration alcohol (4gkg-1d-1) while Control group were instead of water. Food intakes were measured daily. Glucose tolerance test and insulin tolerance test were used to evaluate the self-Detect ability of regulate blood glucose in all stages of alcohol consumption. After the IGT is induced, isletβ-cell functions were tested. After that, animal were sacrificed and its pathological changes in islet were measured. The level of nitric oxide (NO) was estimated by the method of lepoivre[112] and superoxide dismutase (SOD) was assayed utilizing the technique of Kakkar[113]. The apoptosis rate of islet cell was tested by Tunel. NF-κB protein expression situation was also measured by WB.Results:1. IPGTT did not change much in the first two months. IGT shows up after three months alcohol intake and also find fasting glucose has a certain degree of increased[fasting glucose Conrol(4.3±0.32)vs Ethanol(5.1±0.25),p<0.01] as well as insulin secretion function was impaired[fasting insulin Conrol () vs Ethanol (), p <0.01]. Whole body insulin resistance has happened[ITT 2h glucose, Control (0.8±0.16) mmol/l vs Ethanol (2.7±0.51) mmol/l, P <0.05];2. Pathomorphology showed that alcohol caused a large number of inflammatory cell infiltration (neutrophils and eosinophils mainly) in the islets, and a large number of islets has been significantly damaged. The proportion of endocrine department in islet of the alcohol group was substantially reduced [Ins+/Isl (%), Control (70.3±1.44) vs Ethanol (59.4±1.57), P <0.001];3. It seems have a great amount of apoptosis islet cell in Ethanol group [apoptotic rate, Control (15%±3%) vs Ethanol (54%±4%), P <0.001];4. Enzymatic determination of NO and SOD in rats showed that NO was significantly increased in the Ethanol group compared with control group [Control (15.5±1.46) mmol/l vs Ethanol (23.0±2.72) mmol/l, P<0.05], and SOD is significantly reduced in Ethanol group [Control (91.7±2.06) U/ml vs Ethanol (82.1±2.83) U/ml, P <0.05];5. NF-κB protein expression in pancreatic was significantly increased by 389% in alcohol drinking rats, P <0.01.Conclusion:Long-term excessive alcohol consumption in rats can cause IGT and blood glucose increased. And this may caused by the lack of insulin and whole body insulin resistance in ethanol feed rats; The insufficient of insulin in alcohol drinking rats may caused by lack of isletβ-cell, because isletβcells were destroyed by excessive apoptosis and inflammatory cell infiltration; Excessiveβcells apoptosis and inflammatory cell infiltration in islet are possible caused by peroxidation status in the body reflected by NO level, and NO also as a specialized activator to the apoptosis pathway, while NO activate NF-κB pathway leading to exaggerate apoptosis and inflammatory signals; Long-term excessive alcohol intake bring relevant changes to the pancreas which were extraordinary similar as the pathogenesis of type 2 diabetes that happened to the pancreas, So long-term excessive drinking of alcohol can increase in the incidence of type 2 diabetes . |
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