Implying a relatively high ability of NOD mice to detoxify ethanol

Alcohol is taken up by the cells together with glycolipids through endocytosis possibly maintaining the function of solvent during trafficking to the endosomal compartment, hence alcohol facilitated antigen loading may occur both in endosomes and at the cell surface. Interestingly, the alcohol effect was seen only at ethanol concentrations of Torin 1 or more. While higher amounts of alcohol in the blood would be dangerous for most people, the same concentrations would likely be found in the intestine after normal alcohol consumption. Thus, the local levels in the intestine of alcohol consumption may be comparable to those used in vitro. This is of significance since NKT cell are active in the intestinal milieu which plays a role for the diabetes development. NOD mice receiving 5% alcohol in their drinking water display a reduced diabetes incidence and lower blood glucose values at diagnosis. Ethanol given in Trichostatin A doses was well tolerated and did not affect behaviour. In contrast, when mice became diabetic they got more anxious and frightened, moved less, spent less time on the open arms or in the centre of the arena. Such behaviour corresponds to the natural behaviour of prey animal. The dose of ethanol chosen was a compromise avoiding obvious ethanol influence on the liver. Due to the pre-test study the 5% alcohol dosage proved to fulfil this criterion, while this dose still represents a considerable intake of alcohol at least compared to man even after correction for body size. Yet, the ethanol concentration in blood was remarkably low, implying a relatively high ability of NOD mice to detoxify ethanol compared to humans. The start of the study to 6 weeks of age was chosen because evidence of development of insulin resistance exists after treatment with alcohol in rats of younger age. It is important for several treatments for diabetes reduction in NOD mice to start just after weaning or even earlier in life. These considerations have to be compromised. However, a stronger effect of ethanol on diabetes incidence when given earlier in life cannot be ruled out by our present data. In Western culture consumption of alcohol is relatively high, but no clear north-south gradient is seen in Europe as it is for the incidence of T1D.