We have previously observed that treatment of rat islets of Langerhans with interleukin-1 p for 12 h results in nitric oxide-dependent inhibition of insulin secretion, while 48 h treatment increased rates of islet cell death by apoptosis. Here, we demonstrate that interleukin-1 P-mediated nitric oxide formation and inhibition of insulin secretion are significantly reduced by 24 h pretreatment of rat islets of Langerhans with insulin-like growth factor I (IGF-I). IGF-I decreased cytokine induction of nitric oxide synthase in islets. Use of an arginine analogue in culture or IGF-I pretreatment of islets were also effective in protecting islets against cytokine-mediated apoptotic cell death. We conclude that IGF-I antagonises inhibitory and cytotoxic effects of cytokines in rat islets.

Interleukin-1␤ (IL-1␤) treatment of neonatal rat islets19 of a total of 1,600 detectable proteins in GSNOtreated islets (P < 0.01). We conclude 1) that the expression of up to 42 proteins is altered by cytokineinduced or chemically generated NO in the precise experimental conditions chosen and 2) that the majority of proteins altered by prior treatment with IL-1␤ may be the result of NO-independent IL-1␤-mediated regulation of gene expression. This study demonstrates that the combination of 2D gel electrophoresis and mass spectrometry is a powerful tool in the identification of ␤-cell proteins involved in the response to toxic mediators.

Treatment of neonatal rat islets of Langerhans with combined cytokines (interleukin-1L L 10 3IH M, tumour necrosis factor-K K 10 3IH M, interferon-Q Q 5 U/ml) led to extensive cell death, which was potentiated by Fas activation with the anti-Fas cytolytic antibody JO2. Pre-treatment with insulin (25 ng/ml) or insulin-like growth factor-1 (10 3V M) gave only partial protection against cell killing, but prevented the Fas-mediated component. In the absence of cytokine treatment, Fas-mediated killing was not observed.z 1998 Federation of European Biochemical Societies.

By focusing on aspects of morphosyntactic development which are unique to Welsh, we have increased existing about how verbal and nominal morphology are acquired in Welsh-speaking bi-SLI and bi-TD children. The present results point towards productivity problems for Welsh-speaking bi-SLI children who are adversely influenced by low-frequency structures and fail to over-regularize in the context of verbal and nominal concatenating morphology. From a clinical perspective, targeting synthetic past-tense forms through a prompting task may be a promising assessment and intervention tool that future studies could explore further.

The aim of this study was to examine if the growth factor, transforming growth factor beta 1 (TGF beta 1), could prevent induction of nitric oxide synthase and cytokine-mediated inhibitory effects in the insulin-containing, clonal beta cell line RINm5F. Treatment of RINm5F cells for 24 h with interleukin-1 beta (IL-1 beta) (100 pM) induced expression of nitric oxide synthase and inhibited glyceraldehyde-stimulated insulin secretion. Combinations of IL-1 beta (100 pM), tumour necrosis factor-alpha (100 pM) and interferon-gamma (100 pM) reduced RINm5F cell viability (determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium (MTT) reduction assay) and de novo protein synthesis, as measured by incorporation of radiolabelled amino acids into perchloric acid-precipitable protein. Pretreatment of RINm5F cells with TGF beta 1 (10 pM) for 18 or 24 h, prior to the addition of either IL-1 beta or combined cytokines, prevented cytokine-induced inhibition of insulin secretion, protein synthesis and the loss of cell viability. TGF beta 1 pretreatment inhibited cytokine-induced expression and activity of nitric oxide synthase in RINm5F cells as determined by Western blotting and by cytosolic conversion of radiolabelled arginine into labelled citrulline and nitric oxide. Chemically generated superoxide also induced expression of nitric oxide synthase possibly due to direct activation of the nuclear transcription factor NF kappa B, an effect prevented by both an antioxidant and TGF beta 1 pretreatment. In conclusion, the mechanism of action of TGF beta 1 in blocking cytokine inhibitory effects was by preventing induction of nitric oxide synthase.