Insulin-like growth factor I reverses interleukin-1beta inhibition of insulin secretion, induction of nitric oxide synthase and cytokine-mediated apoptosis in rat islets of Langerhans.
We have previously observed that treatment of rat islets of Langerhans with interleukin-1beta 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-1beta-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.
Mabley
J G
JG
Department of Biochemistry, University of Sussex, Falmer, Brighton, UK.
Belin
V
V
John
N
N
Green
I C
IC
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase