Abstract: FRI 485

Sympathetic Synaptic Plasticity Contributes to the Maintenance of Euglycemia during Fasting

Presenter:


Abstract


Hypoglycemia is a serious condition that can lead to loss of consciousness and is potentially fatal. The effects of hypoglycemia are prevented during fasting by the activation of the counter-regulatory response (CRR). Epinephrine secreted from adrenal chromaffin cells contributes to the CRR by increasing hepatic glucose production but how epinephrine secretion is regulated during fasting remains unclear. To address this question we studied the functioning of the sympatho-adrenal system in mice that were fed ad lib or fasted for 1 day. view more

Hypoglycemia is a serious condition that can lead to loss of consciousness and is potentially fatal. The effects of hypoglycemia are prevented during fasting by the activation of the counter-regulatory response (CRR). Epinephrine secreted from adrenal chromaffin cells contributes to the CRR by increasing hepatic glucose production but how epinephrine secretion is regulated during fasting remains unclear. To address this question we studied the functioning of the sympatho-adrenal system in mice that were fed ad lib or fasted for 1 day. As previously reported, urine epinephrine levels were significantly higher after fasting. Blood glucose levels did not differ significantly between fed and fasted littermates, indicating that the CRR could maintain euglycemia even after a substantial period of fasting. Because neuropeptide Y (NPY) is a transmitter that is co-released with epinephrine from chromaffin cells we repeated these experiments in NPY knockout (NPY k/o) mice. In these animals fasting did not increase the urine levels of epinephrine and the mice were hypoglycemic. To determine how the loss of NPY prevented epinephrine release we assessed both pre- and post-synaptic signaling at the preganglionic → chromaffin cell synapse. Post-synaptically, catecholamine release was evoked from chromaffin cells in vitro by a train of voltage clamp depolarizations and monitored using carbon fiber amperometry. There was no difference in the amplitude of amperometric events between fed and fasted wild type (wt) mice. However fasting significantly increased the amplitude of amperometric events in NPY k/o mice, indicating that the catecholamine secretory capacity from isolated cells was negatively regulated by NPY. Because this could not explain the observed decrease in epinephrine release in vivo we next considered whether a presynaptic mechanism was involved. Using acute adrenal slices we found that food deprivation was associated with an increase in the amplitude of the evoked EPSC monitored in chromaffin cells from wt mice. In contrast, the amplitude of the evoked EPSC was reduced in the fasted NPY k/o animals compared to fed littermates. Food deprivation led to a decrease in the paired-pulse ratio (PPR) in wt animals, but to an increase in the PPR in NPY k/o mice, consistent with the involvement of a presynaptic component. Thus food deprivation is associated with an NPY-dependent plasticity at the preganglionic → chromaffin cell synapse. Furthermore, pharmacological inhibition of Y5 receptors blocked the fasting-induced change in synaptic plasticity and epinephrine release, resulting in hypoglycemia. We conclude that NPY, likely secreted from chromaffin cells, increases pre-ganglionic → chromaffin cell synaptic efficacy and this contributes to the maintenance of euglycemia during fasting.

show less
Files:

Share this PosterTalk

About PosterTalks

PosterTalks allows meeting attendees the ability to view these presentations, download or bookmark their favorite presentations, download PDF versions of the posters, ask questions, leave comments, and share presentations with their colleagues – all from the convenience of a smart phone.

Contact Us

Have a question? Click here to contact us. Need technical support? Click here to email support.

© 2018 PosterTalks and Connect BioMed. All other content and data, including data entered into this website are copyrighted by their respective owners.