engleski

Troglitazone increases insulin sensitivity in cultured hepatocytes isolated from rats on high fat diet

Aim/hypothesis. The aim of this study was to elucidate effect of troglitazone on amino acid transport in hepatocytes isolated from rats on high fat diet. Methods. Hepatocytes were isolated by a collagenase perfusion technique. After 24 hours M199 medium were replaced with Hanks-Hepes medium containing a-amino 14C-isobutyric acid to the final concentration of 1 mmol/l with or without of 0.08 mmol/l insulin, or 2 mg/l troglitazone, or 1 mmol/l vanadate, or 0.1 mmol/l phorbol 12- myristate 13-acetate. After one hour hepatocytes were quickly frozen and an aliquot was taken for determination of protein and radioactivity. Results. In hepatocytes obtained from rats on standard diet addition of insulin produced 80% increase of amino acid transport, contrary to those obtained from rats on high-fat diet, where insulin produced only 27% increase of basal amino acid transport. After pre-treatment hepatocytes isolated from rats on standard diet by phorbolester, almost similar reduction of insulin effect was achieved. Vanadate (75%) increased AIB transport in normal hepatocytes and this effect was strongly reduced in resistant cultures. Troglitazone increased and mostly normalised insulin-stimulated transport in hepatocytes isolated from rats on high fat diet as well as in normal hepatocytes pre-treated with phorbolester. Conclusion/interpretation. These findings demonstrate and suggest that troglitazone has an "insulin sensitising" effect on amino acid transport in hepatocytes probably affecting protein kinase C activity.

insulin; insulin resistance; troglitazone; vanadate; TPA; amino acid transport

nije evidentirano