Enhancing Effect of Vasopressin on the Hyperglycemic Response to Carotid Body Chemoreceptor Stimulation

Abstract

Glucose homeostasis, a fundamental process for life, is controlled at multiple levels. Glucose sensitive receptors in the brain, portal vein, liver, pancreas and carotid bodies (Álvarez-Buylla and Roces de Álvarez-Buylla, 1994) provide afferent information to central nervous system (CNS) about the glucose concentration in different regions of the body. In the CNS, this input is integrated by the hypothalamus and the nucleus of the tractus solitarius (NTS) (Adachi et al., 1995). Additionally, there is evidence that carotid body receptors (CBR) are also sensitive to changes in blood glucose concentration (Álvarez- Buylla and Roces de Álvarez-Buylla, 1994; López-Barneo et al., 2001) and afferent impulses from these receptors induce a reflex response on glucose levels: 1) by enhancing glucose production by the liver, and 2 by promoting glucose retention by the brain. Carotid bodies play an important role in the insulin-induced counterregulatory response to mild hypoglycemia (Koyama et al., 2000). The efferent pathway for these reflexes is not fully understood, but previous experiments identify the neurohypophysis and adrenal glands as necessary for the hyperglycemic reflex initiated by NaCN stimulation, and suggest that the effects of these two glands on CBR hyperglycemic reflex are humoral (Álvarez-Buylla et al., 1997). This is supported by the finding that the neurohypophyseal hormone arginine-vasopressin (AVP) has a modulatory role on glucose metabolism during stress, and that an increase of vasopressin plasma levels is observed after perfusion of the carotid sinus with deoxygenated blood, a method similar to NaCN stimulation (Share and Levy, 1966). In addition, hypophysectomy leads to adrenal cortical atrophy and hypoglycemia (Wurtman et al., 1968). We have previously hypothesized that pituitary AVP may be involved in the hyperglycemic reflex initiated by CBR stimulation. In this paper we extend the study to the role of glucose in regulating AVP at the level of NTS (Yarkov et al., 2001), and suggest that this peptide may facilitate hyperglycemic reflexes elicited by CBR stimulation. We show that AVP can directly trigger a hyperglycemic reflex similar to that obtained after CBR stimulation. We suggest that AVP may interact with vasopressin receptors located in the NTS, liver, adrenal cells and pancreas to stimulate the secretion of epinephrine (E) and glucagon.