Alterations in glucose transporter proteins in alcoholic liver disease in the rat.
We used the intragastric feeding rat model for alcoholic liver disease to investigate alterations in glucose transporter isoforms GLUT 1 and GLUT 2 in response to different dietary fats and ethanol. Six groups of rats (three rats/group) were fed ethanol or dextrose with either saturated fat, corn oil, or fish (menhaden) oil. All control animals were pair fed the same diets as ethanol-fed rats except that ethanol was isocalorically replaced by dextrose. In all animals, the following were assessed: pathological changes in the liver, immunohistochemical and Western blot analysis of GLUT 1 and GLUT 2 isoforms, and glycogen distribution. The most severe pathological changes were seen in fish oil/ethanol fed rats, moderate changes were seen in the corn oil/ethanol group and no changes were observed in the dextrose-fed or saturated fat/ethanol groups. In the groups of rats showing pathological liver injury (corn oil/ethanol and fish oil/ethanol), the depletion in liver glycogen was accompanied by decreased GLUT 2 expression and increased GLUT 1 expression. A decrease in glycogen and GLUT 2 expression was also seen in the fish oil/dextrose-fed rats. We hypothesize that the shift in glucose transporters from GLUT 2 to GLUT 1 probably reflects a compensatory response to attenuated gluconeogenic activity and to meet the increased intracellular demand for glucose. This demand for glucose in the presence of depleted glycogen may serve to provide a source for ATP synthesis in the centrilobular zone where hypoxia occurs secondary to ethanol metabolism.
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts 02215.
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Nanji
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Fogt
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Griniuviene
D000818:Animals; D003314:Corn Oil / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004041:Dietary Fats; D005395:Fish Oils; D009004:Monosaccharide Transport Proteins; D000431:Ethanol; D003314:Corn Oil; D006003:Glycogen