Copper Addition Prevents The Inhibitory Effects Of Interleukin 1-Beta On Rat Pancreatic Islets(119 visite) Vinci C, Caltabiano V, Santoro AM, Rabuazzo AM, Buscema M, Purrello R, Rizzarelli E, Vigneri R, Purrello F
Inst. Int. Med., Metab. Endocrinol., University of Catania Medical School, Catania, Italy Inst. the Stud. of Nat. Substances, CNR, Catania, Italy Department of Chemistry, University of Catania, Catania, Italy Cattedra di Endocrinologia, Ospedale Garibaldi, Piazza S. Maria di Gesú, I-95 123 Catania, Italy
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-Iβ (IL-1β), we studied whether Cu(II) addition could prevent the inhibitory effect of IL-1β on insulin release and glucose oxidation in rat pancreatic islets. Islets were incubated with or without 50 U/ml IL-1β, 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/1 (basal insulin secretion) or 16.7 mmol/1 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-1β, 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-1β and Cu-GHL (0.4 μmol/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-1β alone). In contrast to data obtained with Cu(II)-GHL, increasing concentrations of CuSO4 (up to 10 μmol/l) did not influence the inhibitory effect of IL-1β on glucose-stimulated insulin release. Glucose oxidation (in the presence of 16.7 mmol/l glucose) was 31.5 ± 2.4 pmol · isler-1 90min-1 in control islets and 7.0 ± 0.9 (p < 0.01) in IL-1β-exposed islets. In islets exposed to IL-1β and Cu-GHL glucose oxidation was similar to control islets (31.9 ± 1.9). In contrast, Cu-GHL did not prevent the IL-1β-induced increase in nitric oxide production. Nitrite levels were 5 ± 1.7, 26 ± 5 and to 29 ± 4 pmol · islet-1 48 h-1 (mean ± SEM, n = 5) in the culture medium from control, IL-1β and IL-1β + Cu-GHL exposed islets, respectively. These data indicate that the Cu(II) complexed to GHL is able to prevent the inhibitory effects of IL-1β on insulin secretion and glucose oxidation, but not on NO production. The mechanism of action of Cu-GHL is still unclear, but it might restore the activity of the enzymatic systems inhibited by IL-1β.
96 Records (93 escludendo Abstract e Conferenze). Impact factor totale: 394.089 (371.862 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 434.033 (403.635 escludendo Abstract e Conferenze).