Indirect sensing of insulin‐induced hypoglycaemia by the carotid body in the rat

Abstract

The most physiologically important sensors for systemic glucoregulation are located in extracranial sites. Recent evidence suggests that the carotid body may be one such site. We assessed rat carotid body afferent neural output in response to lowered glucose, indirectly by measurement of ventilation, and directly by recording single or few-fibre chemoafferent discharge, in vitro. Insulin (0.4 U kg −1 min −1 )-induced hypoglycaemia (blood glucose reduced by ca 50% to 3.4 ± 0.1 mmol l −1 ) significantly increased spontaneous ventilation (V E ) in sham-operated animals but not in bilateral carotid sinus nerve sectioned (CSNX) animals. In both groups, metabolic rate (measured asV O 2 ) was almost doubled during hypoglycaemia. The ventilatory equivalent (V E /V O 2 ) was unchanged in the sham group leading to a maintained control level of P a,CO 2 , buṫ V E /V O 2 was significantly reduced in the CSNX group, giving rise to an elevation of 6.0 ± 1.3 mmHg in P a,CO 2 . When pulmonary ventilation in sham animals was controlled and maintained, phrenic neural activity increased during hypoglycaemia and was associated with a significant increase in P a,CO 2 of 5.1 ± 0.5 mmHg. Baseline chemoreceptor discharge frequency, recorded in vitro, was not affected, and did not increase when the superfusate [glucose] was lowered from 10 mM to 2 mM by substitution with sucrose: 0.40 ± 0.20 Hz to 0.27 ± 0.15 Hz, respectively (P > 0.20). We suggest therefore that any potential role of the carotid bodies in glucose homeostasis in vivo is mediated through its transduction of some other metabolically derived blood-borne factor rather than glucose per se and that this may also provide the link between exercise, metabolic rate and ventilation.

Effects of fasting on hypoxic ventilatory responses and the contribution of histamine H1 receptors in mice

“…This is not necessarily consistent with previous notions that hypoglycemia stimulates chemoafferent activity, or that it increases _ V E and ventilatory responses to hypoxia or hypercapnia [32][33][34]. The carotid bodies are believed to be important sensors for hypoxia and hypoglycemia, whose action is based on an insulin-induced severe hypoglycemia [35]. However, by using carotid body chemoreceptor cells, Conde et al [36] demonstrated that hypoxia-evoked release of catecholamine and hypoxiainduced action potentials of the carotid sinus nerve were identical under normal and low glucose concentrations.…”

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

“…The responsiveness of mammalian CB cells to hypoglycemia has been confi rmed in the in vitro CB-petrosal ganglion preparation (Zhang et al 2007 ) and in dispersed cat glomus cells (Fitzgerald et al 2009 ). Nonetheless, other authors have failed to fi nd any responsiveness of explanted whole CB preparations to low glucose (Bin-Jaliah et al 2004 ;Conde et al 2007 ) or any signifi cant changes in cytosolic [Ca 2+ ] in dispersed glomus cells in response to rapid glucose removal (Gallego-Martin et al 2012 ). In contrast to these last observations, we have found that, as in the rat (Garcia-Fernandez et al 2007 ), human glomus cells can also depolarize and release transmitters in response to a decrease in the extracellular glucose concentration (Ortega-Saenz et al 2013 ).…”

Effects of low glucose on carotid body chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells

“…In fact, several studies carried out in intact animals have claimed that the CB is indeed a glucose sensor, having a role on glucose homeostasis (2,32,51,54). Unfortunately, there is a nearly even number of studies performed both in intact animals and in intact isolated CB preparations denying the role of chemoreceptor cells as glucoreceptors (1,4,5,11,52). Without neglecting a role for the CB in glucose homeostasis, the concept on contention is the nature of the CB as a glucoreceptor.…”