Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

Sacramento, Joana F.; Chew, Daniel; Melo, Bernardete F.; Donegá, Matteo; Dopson, Wesley; Guarino, Maria P.; Robinson, Alison; Prieto‐Lloret, Jesus; Patel, Sonal; Holinski, Bradley J.; Ramnarain, Nishan; Pikov, Victor; Famm, Kristoffer; Conde, Sílvia V.

doi:10.1007/s00125-017-4533-7

Cited by 58 publications

(76 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and insulin sensitivity were reversed after discontinuation of the electrical stimulus (44). Together, our results put in place the necessary tools to support a potential bioelectronic medicine-based therapeutic approach for Type 2 diabetes.…”

Section: Alternative Therapeutic Approachmentioning

confidence: 63%

“…This approach would bring significant improvement in the standard of care for Type 2 diabetes, requiring minimally invasive procedures and negligible interference with daily activities (6,17). Along with this idea, we have recently demonstrated that the neuromodulation of CSN using kilohertz high frequency alternating current through cuff electrodes surgically placed on the CSN restores metabolic homeostasis in Type 2 diabetes rats (44). These beneficial effects of the neuromodulation of CSN activity on glucose homeostasis 3.…”

Section: Alternative Therapeutic Approachmentioning

confidence: 96%

See 1 more Smart Citation

Carotid body: a metabolic sensor implicated in insulin resistance

Conde

Sacramento

2018

Physiological Genomics

Self Cite

View full text Add to dashboard Cite

The carotid body is now looked at as a multipurpose sensor for blood gases, blood pH, and several hormones. The matter of glucose sensing by the carotid body has been debated for several years in the literature, and these days there is a consensus that carotid body activity is modified by metabolic factors that contribute to glucose homeostasis. However, the sensing ability for glucose is still being pondered: are the carotid bodies low glucose sensors or, in contrast, are they overresponsive in high-glucose conditions? Herein, we debate the glucose and insulin sensing capabilities of the carotid body as key early events in the overactivation of the carotid body, which is increasingly recognized as an important feature of metabolic diseases. Additionally, we dedicate a final section to discuss new outside-the-box therapies designed to decrease carotid body activity that may be used for treating metabolic diseases.

show abstract

Section: Alternative Therapeutic Approachmentioning

confidence: 63%

Section: Alternative Therapeutic Approachmentioning

confidence: 96%

Carotid body: a metabolic sensor implicated in insulin resistance

Conde

Sacramento

2018

Physiological Genomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…; Sacramento et al . ). Knowing from our previous studies the importance of adenosine and ATP as key players in the chemotransduction at the CB, here we investigated the effect of ageing in key proteins involved in the purinergic metabolism in the CB and also the contribution of adenosine and ATP to the CB chemosensory activity.…”

Section: Introductionmentioning

confidence: 97%

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

Sacramento

Olea

Ribeiro

et al. 2019

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Adenosine and ATP are excitatory neurotransmitters involved in the carotid body (CB) response to hypoxia. During ageing the CB exhibits a decline in its functionality, demonstrated by decreased hypoxic responses. In aged rats (20–24 months old) there is a decrease in: basal and hypoxic release of adenosine and ATP from the CB; expression of adenosine and ATP receptors in the petrosal ganglion; carotid sinus nerve (CSN) activity in response to hypoxia; and ventilatory responses to ischaemic hypoxia. There is also an increase in SNAP25, ENT1 and CD73 expression. It is concluded that, although CSN activity and ventilatory responses to hypoxia decrease with age, adjustments in purinergic metabolism in the CB in aged animals are present aiming to maintain the contribution of adenosine and ATP. The possible significance of the findings in the context of ageing and in CB‐associated pathologies is considered. Abstract During ageing the carotid body (CB) exhibits a decline in its functionality. Here we investigated the effect of ageing on functional CB characteristics as well as the contribution of adenosine and ATP to CB chemosensory activity. Experiments were performed in 3‐month‐old and 20‐ to 24‐month‐old male Wistar rats. Ageing decreased: the number of tyrosine hydroxylase immune‐positive cells, but not type II cells or nestin‐positive cells in the CB; the expression of P2X2 and A2A receptors in the petrosal ganglion; and the basal and hypoxic release of adenosine and ATP from the CB. Ageing increased ecto‐nucleotidase (CD73) immune‐positive cells and the expression of synaptosome associated protein 25 (SNAP25) and equilibrative nucleoside transporter 1 (ENT1) in the CB. Additionally, ageing did not modify basal carotid sinus nerve (CSN) activity or the activity in response to hypercapnia, but decreased CSN activity in hypoxia. The contribution of adenosine and ATP to stimuli‐evoked CSN chemosensory activity in aged animals followed the same pattern of 3‐month‐old animals. Bilateral common carotid occlusions during 5, 10 and 15 s increased ventilation proportionally to the duration of ischaemia, an effect decreased by ageing. ATP contributed around 50% to ischaemic‐ventilatory responses in young and aged rats; the contribution of adenosine was dependent on the intensity of ischaemia, being maximal in ischaemias of 5 s (50%) and much smaller in 15 s ischaemias. Our results demonstrate that both ATP and adenosine contribute to CB chemosensory activity in ageing. Though CB responses to hypoxia, but not to hypercapnia, decrease with age, the relative contribution of both ATP and adenosine for CB activity is maintained.

show abstract

“…More recently, Sacramento et al . () demonstrated that bilateral bioelectronic modulation of CSN activity restores insulin sensitivity and glucose tolerance in a rat model of type 2 diabetes suggesting that a bioelectronic medicine approach could bring significant advances to standard care for type 2 diabetes, providing long‐term glucose control and avoiding systemic effects. In this context and for safety purposes, studies are needed to find and refine therapeutic approaches that target the CB to reduce its activity and not to destroy it so that chemoreflex function is preserved.…”

mentioning

confidence: 99%

“…For example, Pijacka et al (2016) found that ATP acting via P2X3 receptors is responsible for the CB hyperactivity and hyperreflexia seen in essential hypertension, supporting the idea of the modulation of P2X3 receptors as a non-surgical strategy to control human hypertension. More recently, Sacramento et al (2018) demonstrated that bilateral bioelectronic modulation of CSN activity restores insulin sensitivity and glucose tolerance in a rat model of type 2 diabetes suggesting that a bioelectronic medicine approach could bring significant advances to standard care for type 2 diabetes, providing long-term glucose control and avoiding systemic effects. In this context and for safety purposes, studies are needed to find and refine therapeutic approaches that target the CB to reduce its activity and not to destroy it so that chemoreflex function is preserved.…”

mentioning

confidence: 99%