Pro-inflammatory cytokines increase glucose, alanine and triacylglycerol utilization but inhibit insulin secretion in a clonal pancreatic beta-cell line.
We have investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines on beta-cell metabolism and insulin secretion using clonal BRIN-BD11 beta cells. Addition of IL-1beta, tumour necrosis factor-alpha and IFN-gamma (at concentrations that did not induce apoptosis) inhibited chronic (24 h) and acute stimulated levels of insulin release (by 59 and 93% respectively), increased cellular glucose and alanine consumption, and also elevated lactate and glutamate release. However, ATP levels and cellular triacylglycerol were decreased while glutathione was increased. We conclude that sub-lethal concentrations of pro-inflammatory cytokines appear to shift beta-cell metabolism away from a key role in energy generation and stimulus-secretion coupling and towards a catabolic state which may be related to cell defence.
Kiely
Aoife
A
School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
McClenaghan
Neville H
NH
Flatt
Peter R
PR
Newsholme
Philip
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000032:analysis / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D005973:Glutamine / Q000032:analysis / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D015638:Cytochalasin D; D019344:Lactic Acid; D018698:Glutamic Acid; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D000409:Alanine