IL-6 is often correlated with many disease states and conditions such as obesity and metabolic syndrome, all marked by abnormal inflammatory mediators. However, given that contracting skeletal muscle produces and releases substantial amounts of the IL-6 then it is likely that this cytokine has positive effects on endocrine regulation. Thus the main objective was to determine the effects of IL-6 on pancreatic beta cell metabolism, insulin secretion, nitric oxide release and redox status. We used a clonal b-cell line (BRIN-BD11) to check these variables in the presence of an exercise IL-6 concentration (50pg/ml) for 24h incubation. BRIN-BD11 cells were maintained in RPMI-1640 tissue culture medium with 10% FCS, 0.1% antibiotics and 11.1mmol/l D-glucose, pH 7.4. Cells were then washed with PBS after which they were incubated in fresh media, containing 11.1mM D-glucose, 2mM L-glutamine, in the absence or presence of IL-6 (50pg/ml) added. After 24h incubation, a media aliquot was removed and used for quantization of insulin, D-glucose, glutamate, urea and nitrites; while the cells were used for the measurement of glutathione metabolism, AMPK/AMPK-P e iNOS expression. After the 24h incubation, the cells were stimulated acutely for 40 min in the presence of 1.1mmol/l glucose followed by 20 min in the presence of 16.7mM glucose and 10mM alanine, when an aliquot of the incubation medium was removed and analyzed for acute insulin secretion. At lest three different experiments were made (*P≤0.05). IL-6 incubations increase insulin secretion over 38% (1379±162ug/mg protein/24h against 994±151ug/mg protein/24h from the control group). Moreover, IL-6 not only increase the chronic insulin secretion but also induced changes in the basal and acute stimulated levels. Basal levels of insulin secretion were increased by almost 100% in the presence of IL-6 (4.8±2ug/mg protein/20min from the control group to 9.6±3.2ug/mg protein/20min with IL-6) indicating an improvement on b-cell sensitivity. AMPK levels were decreased by 75% with a concomitant increased expression of AMPK-P by 84%. We also found a raised iNOS expression together with an intensified nitric oxide production, as measured by nitrite release (0.34±0.12umol nitrite/mg protein/24h from the control groups to 3.59±0.86umol nitrite/mg protein/24h with IL-6 incubation). Both enzyme activities have been suggested as mediators for the increased insulin secretion. IL-6 did not induce redox changes as measured by the glutathione metabolism. Those results indicate that IL-6 can exert positive effects on the b-cell metabolism, protection and function. IL-6 may act as a communication factor between skeletal muscle cells and pancreatic b-cells after exercise, so elevating insulin secretion to achieve optimal concentrations for glucose uptake and metabolism by contracting muscle.
University College Dublin (2009) Proc Physiol Soc 15, C81
Oral Communications: The effect of IL-6 on insulin secretion, nitric oxide release, redox status and signal transduction in a clonal pancreatic beta cell line.
M. D. Krause1,2, P. H. Bittencourt Júnior1, P. Newsholme2
1. Department of Physiology and Department of Physical Education, Federal University of Brazil, Porto Alegre, Rio Grande do Sul, Brazil. 2. UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University Collegue Dublin, Dublin, Ireland.
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Where applicable, experiments conform with Society ethical requirements.