ISSN:
1432-0428
Schlagwort(e):
Key words Copper
;
interleukin-1β
;
islets
;
insulin secretion
;
glucose metabolism
;
nitric oxide.
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary 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/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-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 · islet–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. [Diabetologia (1995) 38: 39–45]
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s001250050251
Permalink
