title: Inorganic nitrite stimulates pancreatic islet blood flow and insulin secretion.
abstract: Reactive nitrogen and oxygen species have been proposed to be involved in control of insulin release from the pancreatic β cell. Recent evidence suggests that the supposedly inert anions nitrate and nitrite are metabolized in blood and tissues to form nitric oxide (NO) and other bioactive nitrogen oxides. Here we present evidence for a novel stimulatory role of nitrite in influencing pancreatic islet physiology via a dual mechanism, involving both indirect enhancement (through microcirculation redistribution) and direct insulinotropic effects on the β cell. In rats, intraperitoneal injection of sodium nitrite increased pancreatic islet blood flow by 50% and serum insulin concentrations by 30%, while whole pancreatic blood flow and glycemia remained unaffected. Nitrite also dose dependently enhanced insulin secretion from rat β cells in vitro under nonstimulatory glucose concentrations. This effect was not mimicked by nitrate and was abolished by the guanylyl cyclase (GC) inhibitor ODQ and the NO scavenger cPTIO. It was also mimicked by a cyclic GMP agonist (8-CPT-cGMP) and a classical NO donor (NONOate). Interestingly, a reactive oxygen species scavenger (vitamin E analog, Trolox) abolished the insulin secretion induced by nitrite. We conclude that nitrite exerts dual stimulatory effects on pancreatic islet function, including enhancement of islet blood flow and subsequent insulin secretion in vivo and direct stimulation of insulin release in vitro. The insulinotropic effect of nitrite is cGMP-dependent and involves formation of reactive nitrogen and oxygen species.
authors: Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, SE-118 83 Stockholm, Sweden.
authors: Thomas
authors: T
authors: Nyström
authors: Henrik
authors: H
authors: Ortsäter
authors: Zhen
authors: Z
authors: Huang
authors: Fan
authors: F
authors: Zhang
authors: Filip J
authors: FJ
authors: Larsen
authors: Eddie
authors: E
authors: Weitzberg
authors: Jon O
authors: JO
authors: Lundberg
authors: Åke
authors: Å
authors: Sjöholm
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007328:Insulin; D009573:Nitrites; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D005947:Glucose