title: Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets.
abstract: Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT). The carotid bodies (CB) are peripheral chemoreceptors that classically respond to hypoxia by increasing chemosensory activity in the carotid sinus nerve (CSN), causing hyperventilation and activation of the sympathoadrenal system. Besides its role in the control of ventilation, the CB has been proposed as a glucose sensor implicated in the control of energy homeostasis. However, to date no studies have anticipated its role in the development of IR. Herein, we propose that CB overstimulation is involved in the etiology of IR and HT, core metabolic and hemodynamic disturbances of highly prevalent diseases like the metabolic syndrome, type 2 diabetes, and obstructive sleep apnoea. We demonstrate that CB activity is increased in IR animal models and that CSN resection prevents CB overactivation and diet-induced IR and HT. Moreover, we show that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB overactivation. We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases.
authors.affiliation: Centro de Estudos de Doenças Crónicas, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria, Lisboa, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ribeiro
authors.forename: Joana F
authors.initials: JF
authors.lastname: Sacramento
authors.forename: Constancio
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Maria P
authors.initials: MP
authors.lastname: Guarino
authors.forename: Emília C
authors.initials: EC
authors.lastname: Monteiro
authors.forename: Sílvia V
authors.initials: SV
authors.lastname: Conde
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000503:physiopathology / Q000601:surgery*; D002346:Carotid Sinus / Q000294:innervation* / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003714:Denervation; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D003345:Corticosterone