Peripheral chemoreceptor deactivation attenuates the sympathetic response to glucose ingestion

Abstract

Acute increases in blood glucose are associated with heightened muscle sympathetic nerve activity (MSNA). Animal studies have implicated a role for peripheral chemoreceptors in this response, but this has not been examined in humans. Heart rate, cardiac output (CO), mean arterial pressure (MAP), total peripheral conductance (TPC), and blood glucose (BG) concentrations were collected in 11 participants. MSNA was recorded in a subset of 5 participants via microneurography. Participants came to the lab on two separate days (i.e. one control and one experimental day). On both days, participants ingested 75g of glucose following baseline measurements. On the experimental day, participants breathed 100% oxygen for 3 minutes at baseline and again at 20, 40, and 60 min post glucose ingestion to deactivate peripheral chemoreceptors. Supplemental oxygen was not given to participants on the control day. There was a main effect of time on blood glucose (P<0.001), heart rate (P<0.001), CO (P<0.001), sympathetic burst frequency (P<0.001), burst incidence (P=0.01), and total MSNA (P=0.001) for both days. Blood glucose concentrations and burst frequency were positively correlated on the control day (r=0.42; P=0.03) and experimental day (r=0.62; P=0.003). There was a time x condition interaction (i.e. normoxia vs. hyperoxia) on burst frequency, in which hyperoxia significantly blunted burst frequency at 20 and 60 min post glucose ingestion only. Given that hyperoxia blunted burst frequency only during hyperglycemia, our results suggest that the peripheral chemoreceptors are involved in activating MSNA post glucose ingestion.

Role of the carotid chemoreceptors in insulin-mediated sympathoexcitation in humans

“…Despite present findings, there is a growing body of literature to support a role for the CB chemoreceptors in glucose regulation (10,11,20,26). The majority of studies examining a role for the carotid chemoreceptors in glucose regulation in humans were carried out in the setting of high insulin (e.g., hyperinsulinemic clamp, mixed meal) (45,55,57). Because of combined changes in both systemic glucose and insulin, it is difficult to fully elucidate the mechanisms and/or factors that may be driving previous findings.…”

“…Present data suggest that the CB chemoreceptors are not necessary for the sympathoexcitatory response to steady-state insulin infusion in healthy humans in the hyperinsulinemic range tested (~50 mg/dL). However, Smorschok et al recently observed an increase in MSNA following glucose ingestion that was attenuated when individuals breathed 100% O 2 acutely (45). Our data would suggest that any role for the CB chemoreceptors in the rise in MSNA is unrelated to their ability to sense and/or respond to increases in plasma insulin commonly seen following glucose ingestion.…”

Sympathetic nervous system activity and reactivity in women with gestational diabetes mellitus

“…Chemoreflex sensitization is a contributing factor to neurovascular dysfunction in many clinical disorders, including heart and renal failure, hypertension and sleep apnea (Kara, Narkiewicz, & Somers, 2003;Prabhakar & Peng, 1985). Evidence have suggested that both glucose (Koyama et al, 2000;Smorschok et al, 2018) and insulin (Limberg, Curry, Prabhakar, & Joyner, 2014) levels play a role in the sensitivity of the chemoreflex during acute and chronic stimulation. For instance, Smorschok et al (2018) found that in non-pregnant populations, the SNA response to glucose ingestion (75 g glucose drink) is blunted (decrease of approximately 35%) with hyperoxia.…”

“…Evidence have suggested that both glucose (Koyama et al, 2000;Smorschok et al, 2018) and insulin (Limberg, Curry, Prabhakar, & Joyner, 2014) levels play a role in the sensitivity of the chemoreflex during acute and chronic stimulation. For instance, Smorschok et al (2018) found that in non-pregnant populations, the SNA response to glucose ingestion (75 g glucose drink) is blunted (decrease of approximately 35%) with hyperoxia. It is important to acknowledge that postprandial glucose/insulin could have remained higher in women with GDM, and therefore, hyperoxia would be more effective in blunting SNA in this population.…”

“…In humans, radiological evidence indicates that the carotid bodies are enlarged in people with diabetes, suggestive of hyperplasia and hyperactivity (Cramer et al, 2014). We have recently shown that the chemoreflex is a contributor to sympathetic activation following glucose ingestion in non-pregnant individuals (Smorschok et al, 2018). Furthermore, ground-breaking work by Ribeiro et al (2013) in a rodent model of diabetes demonstrated that surgical removal of the carotid bodies not only reduced sympathetic nervous activity (SNA), but also prevented insulin resistance as well as subsequent hypertension.…”