Format

Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

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

Abstract

BACKGROUND:

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.

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk