Rostroventrolateral medullary neurons modulate glucose homeostasis in the rat

Abstract

Verberne AJ, Sartor DM. Rostroventrolateral medullary neurons modulate glucose homeostasis in the rat. Am J Physiol Endocrinol Metab 299: E802-E807, 2010. First published August 31, 2010; doi:10.1152/ajpendo.00466.2010.-Several lines of evidence support the view that the premotor sympathetic input to the adrenal gland arises from the rostroventrolateral medulla (RVLM). The aim of this study was to determine whether RVLM neurons play a role in glucose homeostasis. We identified RVLM neurons that control epinephrine secretion by searching for medullospinal neurons that responded to neuroglucoprivation induced by systemic 2-deoxyglucose (2-DG) administration. We tested the effect of disinhibition of the RVLM on arterial blood pressure and plasma glucose concentration. RVLM medullospinal barosensitive neurons (n ϭ 17) were either unaffected or slightly inhibited by 2-DG. In contrast, we found a group (n ϭ 6) of spinally projecting neurons that were excited by 2-DG administration. These neurons were not barosensitive and had spinal conduction velocities in the unmyelinated range (Ͻ1 m/s). These neurons may mediate epinephrine secretion and participate in the counterregulatory responses to neuroglucoprivation. To test the hypothesis that activation of the RVLM leads to adrenomedullary activation and subsequent hyperglycemia, we applied the GABAA antagonist bicuculline to the RVLM and measured blood pressure, heart rate, and blood glucose in rats with intact adrenals or after bilateral adrenalectomy. Disinhibition of the RVLM resulted in hypertension, tachycardia, and hyperglycemia (4.9 Ϯ 0.3 to 14.7 Ϯ 0.9 mM, n ϭ 5, P Ͻ 0.05). Adrenalectomy significantly reduced the hyperglycemic response but did not alter the cardiovascular responses. These data suggest that the RVLM is a key component of the neurocircuitry that is recruited in the counterregulatory response to hypoglycemia. glucose homeostasis; counterregulation; sympathetic nervous system; adrenal glands EPINEPHRINE IS A GLUCOSE-COUNTERREGULATORY HORMONE that is of major importance in countering hypoglycemia in individuals with type 1 and advanced type 2 diabetes (7). Epinephrine is synthesized by chromaffin cells in the adrenal medulla and its secretion is controlled by a distinct group of sympathetic preganglionic neurons (21).It has long been assumed that epinephrine is an important modulator of cardiovascular function, but it probably contributes minimally to blood pressure regulation (38). Indeed, it is likely that its primary role is as a metabolic hormone which serves to mobilise glucose by activation of liver glycogenolysis and gluconeogenesis (13).In contrast to the sympathetic preganglionic neurons that control vasomotor tone, the sympathetic preganglionic neurons that control epinephrine secretion are not particularly responsive to baroreceptor stimulation. Instead, they are strongly activated by neuroglucoprivation induced by administration of the glucoprivic agent 2-deoxyglucose (2-DG) (21), a glucose analog that does not undergo glycolysis. Insulin-i...

C1 neurons: the body's EMTs

“…4). Glucoprivic responses include the release of epinephrine, glucagon, and corticosterone, increased food consumption and GI activity, and decrease in BAT activity (108,147,188). The following evidence implicates the C1 neurons in all of these responses.…”

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

“…Blood glucose levels are also elevated in the OZR due to insulin resistance. However, barosensitive neurons in the RVLM that are likely to be important for regulation of SNA are not responsive to changes in blood glucose (45). The OZR develop hypothyroidism as they reach adulthood (6), and this condition promotes increases in autonomic contributions to MAP and attenuated baroreflexes (12), but the role of the thyroid for obesity-related autonomic dysfunction has not been explored.…”

Orexinergic Activation of Medullary Premotor Neurons Modulates the Adrenal Sympathoexcitation to Hypothalamic Glucoprivation

“…RVLM adrenal sympathetic premotor neurons are mingled with cardiovascular premotor neurons (5). Hence, the RVLM was identified by extracellular recording of cardiovascular sympathetic premotor neurons, which were inhibited by phenylephrine (10 mg/kg i.v.…”

“…; Sigma-Aldrich; Supplementary Fig. 1) (5,19). These neurons were identified after antidromic field-potential mapping of the facial nucleus, elicited by electrical stimulation (0.5 Hz, 0.1 ms, 0.5-1.0 mA) of the facial nerve.…”

“…Previous findings suggest that adrenaline release in response to glucoprivation involves activation of neurons in the perifornical hypothalamus (PeH) and rostral ventrolateral medulla (RVLM). Systemic glucoprivation using 2DG excites RVLM sympathetic premotor neurons (5,6) and orexinergic neurons (7) in the PeH (8). Additionally, neurotropic viruses injected into the adrenal gland transsynaptically label neurons in the RVLM (9) and PeH (10).…”