Abstract
Leptin is a protein hormone that plays a key role in the regulation of energy balance and glucose homeostasis. Leptin and all leptin receptor isoforms are present in the carotid bodies, but its precise function in glucose regulation and metabolism is not yet known. The aim of this study was to determine whether exogenous leptin, microinjected into the commissural nucleus tractus solitarii (cNTS), preceding sodium cyanide (NaCN) injection into the circulatory isolated carotid sinus (ICS), in vivo, modifies hyperglycemic reflex (HR) and brain glucose retention (BGR). In anesthetized Wistar rats (sodium pentobarbital, i.p. 3.3 mg/100 g/saline, Pfizer, Mex), arterial and venous blood samples were collected from silastic catheters implanted in the abdominal aorta and jugular sinus. Exogenous leptin (50 ng/20 nL of aCSF) or leptin vehicle (20 nL of aCSF) microinjected (stereotaxically) into the cNTS 4 min before NaCN (5 μg/100 g/50 μL saline into ICS) (experimental 1 [E1] and control 1[C1] groups, respectively) significantly increased HR and BGR compared with their basal values, but the increase was bigger in the E1 group. When leptin or aCSF were injected into the cNTS before saline (E2 and C2 groups, respectively) glucose responses did not vary when compared with their basal levels. Leptin and its receptors in the cNTS cells probably contribute to their sensitization during hypoxia.
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Alvarez-Buylla R, de Alvarez-Buylla ER (1988) Carotid sinus receptors participate in glucose homeostasis. Respir Physiol 72:347–360
Alvarez-Buylla R, Alvarez-Buylla E, Mendoza H, Montero SA, Alvarez-Buylla A (1997) Pituitary and adrenals are required for hypoglycemic reflex initiated by stimulation of CBR with cyanide. Am J Physiol (Reg Integr Comp Physiol) 272:R92–R399
Alvarez-Buylla R, Huberman A, Montero S, Lemus M, Valles V, de Alvarez-Buylla ER (2003) Induction of brain glucose uptake by a factor secreted into cerebrospinal fluid. Brain Res 994:24–133
Ciriello J, Caverson M (2014) Carotid chemoreceptor afferent projections to leptin receptor containing neurons in nucleus of the solitary tract. Peptides 58:30–35
Ciriello J, Moreau JM (2013) Systemic administration of leptin potentiates the response of neurons in the nucleus of the solitary tract to chemoreceptor activation in the rat. Neurosci 229:887–899
Cowan A, Lewis JW, Macfarlane IR (1977) Agonist and antagonist properties of buprenorphine, a nociceptive agent. Br J Pharmacol 60:537–545
Denroche H, Huynh F, Kieffer T (2012) The role of leptin in glucose homeostasis. J Diabetes Invest 3:115–129
Elmquist JK, Elias CF, Saper CB (1999) From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22:221–232
García-Jiménez S, Bernal G, Martínez SMF, Monroy NA, Jaimes TC, Meneses AA et al (2015) Serum leptin is associated with metabolic syndrome in obese Mexican subjects. J Clin Lab Anal 29:5–9
Gavrilova O, Marcus-Samuels B, Graham D, Kim JK, Shulman GI, Castle AL et al (2000) Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 105:271–278
Huo L, Grill HJ, Bjorbaek C (2006) Divergent regulation of propiomelanocortin neurons by leptin in the nucleus of the solitary tract and the arcuate hypothalamic nucleus. Diabetes 55:567–573
Lemus M, Montero S, Leal C, Portilla de Buen E, Luquin S, García J et al (2011) Nitric oxide infused in the solitary tract nucleus blocks brain glucose retention induced by carotid chemoreceptor stimulation. Nitric Oxide 25:385–395
Liu L, Karkanis GB, Hawkins M, Barzilai N, Wang L, Rossetti L (1998) Intracerebroventricular leptin regultes hepatic but not peripheral glucose fluxes. J Biol Chem 273:31160–31167
McNay EC, Sherwin RS (2004) From artificial cerebro-spinal fluid (aCSF) to artificial extracellular fluid (aECF): microdialysis perfusate composition effects on in vivo brain ECF glucose measurements. J Neurosci Methods 132:35–43
Messenger SA, Moreau JM, Ciriello J (2013) Effect of chronic intermittent hypoxia on leptin and leptin receptor protein expression in the carotid body. Brain Res 1513:51–60
Mizuno A, Murakami T, Otani S, Kuwajima M, Shima K (1998) Leptin affects pancreatic endocrine functions through the sympathetic nervous system. Endocrinol 139:3863–3870
Montero S, Yarkov A, Álvarez-Buylla R (2000) Carotid chemoreceptors participation in brain glucose regulation. Adv Exp Med Biol 475:749–760
Morton GJ, Schwartz MW (2011) Leptin and the central nervous system control of glucose metabolism. Physiol Rev 91:389–411
Park S, Ahn IS, Kim da S (2010) Central infusion of leptin improves insulin resistance and suppresses b-cell function, but notb-cell mass, primarily through the sympathetic nervous system in a type 2 diabetic rat model. Life Sci 86:854–862
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic, NewYork
Ueki M, Linn F, Hossmann K-A (1988) Functional activation of cerebral blood flow and metabolism before and after global ischemia of rat brain. J Cereb Blood Flow Metab 8:486–494
Uotani S, Bjørbaek C, Tornøe J, Flier JS (1999) Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downreg‑ulation. Diabetes 48:279–286
Wjidan K, Ibrahim E, Caszo B, Gnanou J, Singh H (2015) Dysregulation of glucose homeostasis following chronic exogenous administration of leptin in healthy Sprague-Dawley rats. JCDR 9:OF06–OF09
Acknowledgements
Our work was supported by Consejo Nacional de Ciencia y Tecnología, México (CB20121-177047).
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Lemus, M., Mojarro, C., Montero, S., Melnikov, V., Ramírez-Flores, M., de Álvarez-Buylla, E.R. (2018). Leptin in the Commissural Nucleus Tractus Solitarii Increases the Glucose Responses to Carotid Chemoreceptors Activation by Cyanide. In: Gauda, E., Monteiro, M., Prabhakar, N., Wyatt, C., Schultz, H. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 1071. Springer, Cham. https://doi.org/10.1007/978-3-319-91137-3_18
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DOI: https://doi.org/10.1007/978-3-319-91137-3_18
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