Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats.
Moderate amounts of alcohol intake have been reported to have a protective effect on the cardiovascular system and this may involve enhanced insulin sensitivity. We established an animal model of increased insulin sensitivity by low ethanol consumption and here we investigated metabolic parameters and molecular mechanisms potentially involved in this phenomenon. For that, Wistar rats have received drinking water either without (control) or with 3% ethanol for four weeks. The effect of ethanol intake on insulin sensitivity was analyzed by insulin resistance index (HOMA-IR), intravenous insulin tolerance test (IVITT) and lipid profile. The role of liver was investigated by the analysis of insulin signaling pathway, GLUT2 gene expression and tissue glycogen content. Rats consuming 3% ethanol showed lower values of HOMA-IR and plasma free fatty acids (FFA) levels and higher hepatic glycogen content and glucose disappearance constant during the IVITT. Neither the phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), nor its association with phosphatidylinositol-3-kinase (PI3-kinase), was affected by ethanol. However, ethanol consumption enhanced liver IRS-2 and protein kinase B (Akt) phosphorylation (3 times, P<0.05), which can be involved in the 2-fold increased (P<0.05) hepatic glycogen content. The GLUT2 protein content was unchanged. Our findings point out that liver plays a role in enhanced insulin sensitivity induced by low ethanol consumption.
Tomie Furuya
Daniela
D
Dept. of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo. Av. Prof. Lineu Prestes 1524, 05508-900 Sao Paulo, Brazil.
Binsack
Ralf
R
Onishi
Mary Emy
ME
Monteiro Seraphim
Patricia
P
Fabres Machado
Ubiratan
U
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D051273:Glucose Transporter Type 2; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D002784:Cholesterol; D000431:Ethanol; D005230:Fatty Acids, Nonesterified; D051273:Glucose Transporter Type 2; D006003:Glycogen; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins; D009004:Monosaccharide Transport Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D014280:Triglycerides; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C494920:Akt1 protein, rat