Carotid body, insulin, and metabolic diseases: unraveling the links

Abstract

The carotid bodies (CB) are peripheral chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Hypoxia, hypercapnia, and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS) activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnea (OSA) is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH) and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

“…; Conde et al . ). Such sympatho‐excitation not only contributes to increased cardiac stress and arrhythmia formation, but also hypertension, impaired renal function and the development of insulin resistant diabetes.…”

Insulin resistance: a new consequence of altered carotid body chemoreflex?

“…; Conde et al . ). Moreover, we have shown that bilateral CSN resection prevents the development of these features (Ribeiro et al .…”

“…As a whole, data reflect that CB dysfunction is implicated in the pathophysiology of various human cardiovascular diseases through the modulation of the SNS. Additionally, in the last couple of years, a new line of research has emerged from our laboratory, linking the CB-mediated sympathetic nerve activation to metabolic diseases (Ribeiro et al 2013;Conde et al 2014).…”

Possible Hypoxia Signaling Induced Alteration of Glucose Homeostasis in Rats Exposed to Chronic Intermittent Hypoxia - Role of Antioxidant (Vitamin C) and Ca2+ Channel Blocker (Cilnidipine)

“…Increase in generation of ROS due to CIH emphasized an impairment in beta cell function although the present study did not reveal any changes in insulin level due to CIH. Hence it may be attributed purely on decrease insulin sensitivities supported by increase HOMA-IR and insulinogenic-index in present study [7,33] In conclusion, it may be stated that CIH induces impaired insulin sensitivities and resultant hyperglycemia by either direct or through HIF-1 . This disturbed glucose homeostasis may be remodeled by antioxidant like vitamin C or Ntype calcium channel blocker like cilnidipine treatment.…”