EFFECTS OF TUMOR NECROSIS FACTOR-alfa ON AMINO ACID TRANSPORT AND GLUCONEGENSIS IN HEPATOCYTES CULTURED IN VITRO (CROSBI ID 504218)
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Alan Gadžić ; Jagoda Roša ; Josip Roša
engleski
EFFECTS OF TUMOR NECROSIS FACTOR-alfa ON AMINO ACID TRANSPORT AND GLUCONEGENSIS IN HEPATOCYTES CULTURED IN VITRO
It has been suggested that tumor necrosis factor alpha (TNF-alfa) play a pivotal role in the pathogenesis of insulin resistance. Furthermore, TNF-alfa could act directly on the liver, or indirectly by stimulating lipolysis in fat cells thereby increasing systemic NEFA concentrations. The aim of this study was to determine whether TNF-alfa has direct effects on the liver and to find possible implications for the pathogenesis of insulin resistance. Therefore, we studied short-time (4 h) and long-time (24 h) action of TNF-alfa on amino acid transport and gluconeogenesis in cultured rat hepatocytes. We also studied the role of protein kinase C (PKC) in insulin signaling and TNF-alfa action. Hepatocytes were isolated by a modified collagenase perfusion technique from Wistar rats and cultured for 24 h in M 199 medium with or without TNF-alfa (17 ng/ml medium). In the presence of insulin (80 nmol/l) basal alfa-amino isobutyric acid (AIB) uptake was increased for 70%. TNF-alfa during short-time (4 h) incubation did not change basal AIB transport, but significantly (25%) increased insulin-stimulated AIB transport, and also did not affect basal or glucagon-stimulated gluconeogenesis. In contrast, after long-time (24 h) treatment with TNF-alfa glucagon-stimulated gluconeogenesis was increased for 80 %. This effects of TNF-alfa was ameliorated by phorbol ester treatment (0, 1 mmol/l phorbol 12-myristate 13-acetate). These results indicated that PKC activation is important in insulin signaling and TNF-alfa action. Furthermore, it has been shown that TNF-alfa can act directly on the liver cells and modulate insulin action, suggesting his implications as an important regulator of insulin sensitivity, but not by causing insulin resistance.
amino acid transport; cultured hepatocytes; gluconeogenesis; insulin resistance; tumor necrosis factor alpha (TNF-alfa)
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83-84-x.
2004.
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FEBS Lecture Course on cellular Signaling & 4th Dubrovnik Signaling Conference
Đikić Ivan, Husnjak Koraljka
Zagreb:
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FEBS lecture course on cellular signaling & 4th Dubrovnik signaling conference
poster
21.05.2004-27.05.2004
Dubrovnik, Hrvatska