Effects of nitric oxide synthase blockade on dorsal vagal stimulation-induced pancreatic insulin secretion

We and others have previously shown that the dorsal motor nucleus of the vagus (DMV) is involved in regulation of pancreatic exocrine secretion. Many pancreatic preganglionic neurons within the DMV are inhibited by pancreatic secretagogues suggesting that an inhibitory pathway may participate in the control of pancreatic exocrine secretion. Accordingly, the present study examined whether chemical stimulation of the DMV activates the endocrine pancreas and whether an inhibitory pathway is involved in this response. All experiments were conducted in overnight fasted isoflurane/urethane-anesthetized Sprague Dawley rats. Activation of the DMV by bilateral microinjection of bicuculline methiodide (BIM, GABA(A) receptor antagonist, 100 pmol/25 nl; 4 mM) resulted in a significant and rapid increase in glucose-induced insulin secretion (9.2±0.1 ng/ml peak response) compared to control microinjection (4.0±0.6 ng/ml). Activation of glucose-induced insulin secretion by chemical stimulation of the DMV was inhibited (2.1±1.1 ng/ml and 1.6±0.1 ng/ml 5 min later) in the presence of the muscarinic receptor antagonist atropine methonitrate (100 μg/kg/min, i.v.). On the other hand, the nitric oxide (NO) synthesis inhibitor l-nitroarginine methyl ester (30 mg/kg, i.v.) significantly increased the excitatory effect of DMV stimulation on glucose-induced insulin secretion to 15.3±3.0 ng/ml and 16.1±3.1 ng/ml 5 min later. These findings suggest that NO may play an inhibitory role in the central regulation of insulin secretion.