CNS modulation of pancreatic endocrine function

Abstract

The involvement of the CNS in pancreatic hormone release has been studied. 1.) It has been shown that one source of vagal efferent fibers cap-able of facilitating insulin secretion originated in the rostral half of the nucleus ambiguus. 2.) Acute lesions of the ventromedial hypothalamus resulted in hyperinsulinaemia that could be abolished by acute vagotomy. 3.) Chronic lesions of the ventromedial hypothalamus increased secretion of insulin and glucagon, and decreased secretion of somatostatin when the pancreas was subsequently isolated and perfused. These changes were attributed to altered cholinergic activity related to previous ventromedial hypothalamic lesions as they could be reversed toward normal by atropine infusion or mimicked by the cholinergic agonist, methacholine. 4.) Electrical stimulation of the lateral hypothalamus in anaes-thetized rats produced both an inhibitory component of insulin secretion, probably related to adrenergic stimulation, and a stimulatory component, probably due to the release into the blood of factor(s) that promote insulin secretion. 5.) The anatomical organi-zation of brain of the genetically obese (oh~oh) mice is abnormal. These abnormalities could be involved in the endocrinological disturbances of these animals. Key words: Acute ventromedial hypothalamic lesions (VMH), chronic VMH lesions, lateral hypothalamus stimulation, nucleus ambiguus stimu-lation, insulin secretion, glucagon secretion, somato-statin secretion, brain organization of obese (oh~oh) mouse Humoral factors such as metabolic substrates, together with systemically or locally released hor-mones, are major secretagogues for the control of insulin and glucagon secretion from the endocrine pancreas. However, considerable evidence suggests a neural contribution to the control of the endocrine pancreas as well. The autonomic nervous system via the vagus and splanchnic nerves probably provides the anatomical basis for the efferent innervation of the pancreas [33]. Indeed, a vagal facilitatory [5] and a splanchnic inhibitory [27] modulation of insulin release has been demonstrated with the in situ per-fused pancreas preparation, a preparation that allows direct neural stimulation to be studied under control-led perfusion (substrate) conditions. Both the vagal and splanchnic innervation of the pancreas have been shown to contribute to hormone secretion under phy-siological conditions known to depend on neural sen-sory afferent information. Thus, the early rise in insu-lin levels after oral ingestion appears to be gustatory-evoked via oropharyngeal sensory afferent nerves [7] and is absent in animals previously vagotomized sub-diaphragmatically [26]. A rapid rise in glucagon and a suppression of insulin release accompany a fall in systemic blood pressure that is dependent on sinus nerve baroreceptor afferents and splanchnJ[c nerve connections to the pancreas [21]. Furthermore, splanchnic nerve transection elevates basal insulin levels more markedly under hypoglycaemic than under normoglycaemic conditions [27]. The above examples serve to illustrate that both major branches of the autonomic nervous system contribute to the control of pancreatic hormone release; however, the sites for integration and modu-lation of such autonomic efferent outputs within the central nervous system (CNS) are not well under-stood. The following paper summarizes much of the work done in our laboratory directed towards under-standing the involvement of the CNS in pancreatic hormone release.