ANF inhibits glucose-stimulated insulin secretion in mouse and rat.

Atrial natriuretic factor (ANF) is synthesized in atrial cells and was recently demonstrated to also occur within islet glucagon cells. Therefore, we investigated the possible effects of synthetic rat ANF-(1-28) on basal and stimulated insulin and glucagon secretion in the mouse and on glucose-induced insulin secretion in the rat. We found that ANF did not affect basal levels of insulin, glucagon, or glucose when injected intravenously at dose levels between 0.25 and 4.0 nmol/kg in mice. However, when injected together with glucose (2.8 mmol/kg), ANF (4.0 nmol/kg) inhibited the increase in plasma insulin levels by 40%, from 114 +/- 8 microU/ml in controls to 81 +/- 8 microU/ml (P less than 0.01). Likewise, the increase in plasma insulin levels during an intravenous infusion of glucose in rats (10 mg/min) was significantly reduced by ANF (100 pmol.kg-1.min-1; P less than 0.001). In contrast, the increase in plasma levels of insulin and glucagon after the intravenous injection of the cholinergic agonist carbachol in mice (0.16 mumol/kg) was not significantly affected by ANF. We conclude that ANF inhibits glucose-stimulated insulin secretion in the mouse and the rat. The peptide may therefore be a modulator of insulin secretion.