engleski

Effects of tumor necrosis factor-alfa on glucose production in hepatocytes cultured in vitro

Background and purpose: Insulin resistance is a common phenomenon in obesity and type 2 diabetes. A number of factors have been suggested as possible linking between insulin resistance and type 2 diabetes and TNF-alfa is one of them . The aim of this study was to investigate the possible direct action of TNF-alfa on basal as well as glucagon stimulated glucose production in cultured rat hepatocytes. Materials and methods: Hepatocytes were isolated by a collagenase perfusion technique and cultured for 24 h in M 199 serum-free medium. The glucose production was measured by incubating the cultures in glucose-free Hanks-Hepes medium with addition 10 mmol/l pyruvate. The glucose released into the medium was determined enzymatically with glucose oxidase. Results: The addition TNF-alfa during short time period (4h) did not change basic as well as glucagon stimulated glucose production. TNF-alfa alone, given through long time period (24 h) significantly (p<0, 01) but little increased basic glucose production. On the other hand glucagon, given through long time pre-treatment period increased glucose production more than 150% after 3-hours incubation period. TNF-alfa together with glucagon produced more than 200% increase of glucose production at end of the same incubation period. Conclusion: Increasing basic, as well as glucagon stimulated gluconeogenesis was a direct effect of TNF-alfa in liver during long time period, which could be responsible for development fasting hyperglycemia and insulin resistance.

Insulin; insulin resistance; glucagon; glucose production; gluconeogenesis; TNF-alfa

nije evidentirano