Copper addition prevents the inhibitory effects of interleukin 1-beta on rat pancreatic islets.
Since copper [Cu(II)] is a necessary cofactor for both intra-mitochondrial enzymes involved in energy production and hydroxyl scavenger enzymes, two hypothesised mechanisms for action of interleukin-I beta (IL-1 beta), we studied whether Cu(II) addition could prevent the inhibitory effect of IL-1 beta on insulin release and glucose oxidation in rat pancreatic islets. Islets were incubated with or without 50 U/ml IL-1 beta, in the presence or absence of various concentrations of Cu(II)-GHL (Cu(II) complexed with glycyl-L-histidyl-L-lysine, a tripeptide known to enhance copper uptake into cultured cells). CuSO4 (1-1000 ng/ml) was used as a control for Cu(II) effect when present as an inorganic salt. At the end of the incubation period, insulin secretion was evaluated in the presence of either 2.8 mmol/l (basal insulin secretion) or 16.7 mmol/l glucose (glucose-induced release). In control islets basal insulin secretion was 92.0 +/- 11.4 pg.islet-1 h-1 (mean +/- SEM, n = 7) and glucose-induced release was 2824.0 +/- 249.0 pg.islet-1 h-1. In islets pre-exposed to 50 U/ml IL-1 beta, basal insulin release was not significantly affected but glucose-induced insulin release was greatly reduced (841.2 +/- 76.9, n = 7, p < 0.005). In islets incubated with IL-1 beta and Cu-GHL (0.4 mumol/l, maximal effect) basal secretion was 119.0 +/- 13.1 pg.islet-1 h-1 and glucose-induced release was 2797.2 +/- 242.2, (n = 7, p < 0.01 in respect to islets exposed to IL-1 beta alone).(ABSTRACT TRUNCATED AT 250 WORDS)
Vinci
C
C
Institute of Internal Medicine, Metabolism and Endocrinology, University of Catania Medical School, Italy.
Caltabiano
V
V
Santoro
A M
AM
Rabuazzo
A M
AM
Buscema
M
M
Purrello
R
R
Rizzarelli
E
E
Vigneri
R
R
Purrello
F
F
D000818:Animals; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D019327:Copper Sulfate; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D009842:Oligopeptides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000378:metabolism
D007328:Insulin; D007375:Interleukin-1; D009842:Oligopeptides; D011994:Recombinant Proteins; D009569:Nitric Oxide; C020905:glycyl-histidyl-lysine; D003300:Copper; D013482:Superoxide Dismutase; D005947:Glucose; D019327:Copper Sulfate