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Int J Obes Relat Metab Disord. 2001 Jul;25(7):1018-26.

TNFalpha and leptin inhibit basal and glucose-stimulated insulin secretion and gene transcription in the HIT-T15 pancreatic cells.

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  • 1Hellenic National Diabetes Centre (HNDC), Athens, Greece.



Tumor necrosis factor alpha (TNFalpha), a cytokine produced at inflammatory sites and in adipose tissue, is known primarily for its detrimental effects on insulin action. There is evidence to suggest that TNFalpha may also influence beta-cell function. Leptin is another adipose tissue-derived hormone that might also act on beta-cells.


We explored the independent and combined effects of TNFalpha and leptin upon basal and glucose-stimulated insulin transcription and secretion in the HIT-T15 pancreatic beta cell line.


Cells were cultured for 40 h in the presence of near-normal basal (7 mM) or high (16.7 mM) glucose and treated with either TNFalpha (1, 10 and 50 ng/ml) or leptin (10, 50 and 100 ng/ml) or both together. Insulin concentrations were measured by radioimmunoassay. Insulin mRNA levels were evaluated by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method, after normalization with beta-actin mRNA.


TNFalpha significantly suppressed basal and glucose-stimulated insulin secretion and proinsulin mRNA transcription in a dose-dependent manner, an effect that was more powerful in the presence of high glucose. Leptin also inhibited dose-dependent insulin mRNA and protein at both glucose concentrations, but did not appear to further potentiate the suppressive effects of TNFalpha.


TNFalpha suppresses both basal and glucose-stimulated insulin transcription and secretion in HIT-T15 cells, an effect that is enhanced significantly by high glucose. Leptin also independently inhibits basal and glucose-stimulated insulin secretion and transcription but does not modify TNFalpha effects. These effects might contribute to the abnormalities of glucose metabolism that characterize conditions of increased TNFalpha and/or leptin production.

[PubMed - indexed for MEDLINE]
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