Effects of tumor necrosis factor-alpha on insulin stimulated amino acid transport in cultured rat hepatocytes.
It has been suggested that tumor necrosis factor alpha (TNF-alpha) plays a pivotal role in the pathogenesis of insulin resistance. It could act directly or indirectly in liver. The aim of this study was to determine direct short time (4 h) and long time (24 h) action of TNF-alpha on amino acid transport in cultured rat hepatocytes and possible role of protein kinase C (PKC) in insulin signal pathway and insulin resistance. Hepatocytes were isolated by a modified collagenase perfusion technique and cultured for 24 h in M 199 medium. In the presence of insulin basal alpha-amino isobutyric acid (AIB) uptake was increased 55%. TNF-alpha in short time action did not change basal AIB transport, but significantly (25%) increased insulin stimulated uptake. Short time action of TNF-alpha was ameliorated by phorbol ester treatment. These results indicated that PKC activation is important in insulin signaling and TNF-alpha action. TNF-alpha acting directly did not cause insulin resistance in cultured hepatocytes.
Rosa
Jagoda
J
Department of Physiology, School of Dentistry, University of Zagreb, Croatia. jrosa@mef.hr
Baraba
Anja
A
Rosa
Josip
J
D000596:Amino Acids / Q000493:pharmacokinetics*; D000818:Animals; D018929:Cell Culture Techniques; D022781:Hepatocytes / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000596:Amino Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C