Tetrahydrobiopterin synthesis precedes nitric oxide-dependent inhibition of insulin secretion in INS-1 rat pancreatic beta-cells.
Interleukin 1 (IL-1) induces pancreatic beta-cell dysfunction mainly due to overproduction of nitric oxide (NO). Since tetrahydrobiopterin (BH4) is a obligatory cofactor of NO synthases, we examined the temporal relationship of BH4 synthesis, NO production and insulin secretion in a pancreatic beta-cell line (INS-1) which was exposed to IL-1. IL-1 affected BH4 synthesis in a time- and concentration-dependent manner. At a concentration of 10 ng/ml IL-1 caused an increase in intracellular BH4 with peak levels being observed at 6 hours followed by a steady decline in the cellular BH4 content. The increase in BH4 synthesis was followed by enhanced NO production and, consecutively, inhibition of insulin secretion. The concentration-dependent regulation of BH4 synthesis, NO production and suppression of insulin secretion indicate a functional link between these parameters in pancreatic beta-cells.
Laffranchi
R
R
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Schoedon
G
G
Blau
N
N
Spinas
G A
GA
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D014407:Tumor Cells, Cultured
D007328:Insulin; D001708:Biopterins; D009569:Nitric Oxide; C003402:sapropterin