Effects of nitric oxide synthase inhibition on dorsal vagal stimulation‐induced pancreatic insulin secretion

Abstract

Pancreatic islets receive parasympathetic input from the dorsal motor nucleus of the vagus (DMV). This study examined whether chemical activation of the DMV modulates pancreatic endocrine secretion and whether this process involves nitric oxide (NO). All experiments were conducted in isoflurane/urethane-anaesthetized Sprague Dawley rats after over-night fast. Stimulation of the DMV using bicuculline (Bic; GABAA antagonist, 100 pmol/25 nl) microinjections resulted in significant and rapid increases in glucose-mediated insulin secretion (9.2 ± 0.1 ng/ml peak) compared to vehicle (5.5 ± 2.0 ng/ml; P<0.05). A repeat microinjection of BIM made 40 min later did not increase insulin secretion significantly. Microinjection of Bic outside the DMV or microinjection of vehicle into the DMV did not affect insulin secretion. Blockade of muscarinic receptors (atropine methonitrate; 100μg/kg min, i.v. for 20 minutes) reduced the activation of glucose-mediated insulin secretion produced by stimulation of the DMV from 9.2 ± 0.9 ng/ml to 1.6 ± 0.1 ng/ml (P<0.05). On the other hand, L-nitroarginine (NO synthase inhibitor, 30 mg/kg, i.v.) increased the excitatory effect of DMV stimulation on glucose-mediated insulin secretion (from 8.9 ± 1.2 ng/ml to 15.3 ± 3.0 ng/ml; P<0.05). This suggests that NO may play an inhibitory role in the vagal regulation of pancreatic endocrine secretion. Supported by AHMRF.