Hypoglycemia-induced noradrenergic activation in the VMH is a result of decreased ambient glucose

Vries, Martin G. de; Lawson, Marcus A.; Beverly, J. Lee

doi:10.1152/ajpregu.00403.2005

Cited by 34 publications

(42 citation statements)

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“…While one study has shown that the source of norepinephrine in humans is primarily adrenomedullary (9), data from animal models suggest that central regulation of sympathetic output may be more complicated and organ specific (21). For example, increased levels of norepinephrine have been found within the brain during hypoglycemia, specifically in the paraventricular (11,26) and ventromedial nuclei (10), and despite reduced systemic levels, these hypothalamic levels were not reduced after multiple daily episodes of hypoglycemia (11). These authors postulated that the mechanism for blunted sympathoadrenal responses with repeated hypoglycemia occurs downstream from the hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

“…Am J Physiol Endocrinol Metab 293: E1511-E1516, 2007. First published October 16, 2007; doi: 10.1152/ajpendo.00340.2007.-The aim of this study was to test the hypothesis that antecedent short-term administration of estradiol or progesterone into the central nervous system (CNS) reduces levels of neuroendocrine counterregulatory hormones during subsequent hypoglycemia. Conscious unrestrained male Sprague-Dawley rats were studied during randomized 2-day experiments.…”

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confidence: 99%

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Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

Sandoval¹,

Gong²

2007

American Journal of Physiology-Endocrinology and Metabolism

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aim of this study was to test the hypothesis that antecedent short-term administration of estradiol or progesterone into the central nervous system (CNS) reduces levels of neuroendocrine counterregulatory hormones during subsequent hypoglycemia. Conscious unrestrained male Sprague-Dawley rats were studied during randomized 2-day experiments. Day 1 consisted of an 8-h lateral ventricle infusion of estradiol (1 g/l; n ϭ 9), progesterone (1 g/l; n ϭ 9), or saline (0.2 l/min; n ϭ 10). On day 2, a 2-h hyperinsulinemic (30 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) hypoglycemic (2.9 Ϯ 0.2 mM) clamp was performed on all rats. Central administration of estradiol on day 1 resulted in significantly lower plasma epinephrine levels during hypoglycemia compared with saline, whereas central administration of progesterone resulted in increased levels of plasma norepinephrine and decreased levels of corticosterone both at baseline and during hypoglycemia. Glucagon responses during hypoglycemia were unaffected by prior administration of estradiol or progesterone. Endogenous glucose production following day 1 estradiol was significantly lower during day 2 hypoglycemia, and consequently, the glucose infusion rate to maintain the glycemia was significantly greater after estradiol administration compared with saline. These data suggest that 1) CNS administration of both female reproductive hormones can have rapid effects in modulating levels of counterregulatory hormones during subsequent hypoglycemia in conscious male rats, 2) forebrain administration of reproductive hormones can significantly reduce pituitary adrenal and sympathetic nervous system drive during hypoglycemia, 3) reproductive steroid hormones produce differential effects on sympathetic nervous system activity during hypoglycemia, and 4) reduction of epinephrine resulted in significantly blunted metabolic counterregulatory responses during hypoglycemia. epinephrine; sex differences; reproductive hormones WOMEN, COMPARED WITH MEN, have reduced autonomic responses to psychological stress (22), exercise (8,19,40), and hypoglycemia (14). We have previously shown that women taking estrogen replacement therapy have reduced autonomic counterregulatory activity in response to insulin-induced hypoglycemia compared with age-and body mass index-matched men and women not taking estrogen replacement therapy (35), thus suggesting that chronic elevations in estradiol may be an important mechanism for sexually dimorphic responses to stress.Previous studies have demonstrated that estrogen can have rapid biological effects in the brain and periphery (15,25,31,41). Whether these rapid effects are mediated through the classical estrogen receptors (estrogen receptor-␣ and/or -␤) or nongenomic mechanisms is not understood. In vitro estradiol increases intracellular signaling within minutes (23). In vivo, both centrally and peripherally administered estrogen increases intracellular signaling within the hypothalamus at 6 and 24 h after injection. These signaling changes may mediate a variety of physiological c...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

Sandoval¹,

Gong²

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Blood glucose levels in rats are typically around 5-6 mM (de Vries et al, 2003(de Vries et al, , 2005. However, in anesthetized animals these levels are reported to increase 2-fold (Moon et al, 2013).…”

Section: Basal Glucose Levelsmentioning

confidence: 99%

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device

Cordeiro

Vries

Ngabi

et al. 2015

Biosensors and Bioelectronics

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“…The concentration of extracellular glucose in the VMH is 20 -25% of plasma glucose under euglycemic conditions and generally declines in parallel with plasma glucose during hypoglycemia (8). When VMH glucose was maintained during systemic hypoglycemia, peripheral sympathoadrenal responses were attenuated (3,10), demonstrating that the reduction of glucose within the VMH is both required and sufficient for activation of CRR. Activation of noradrenergic systems in the VMH increased sympathetic nervous system activity, a mediator of glucose mobilization (31), and there is an increase in NE release in the VMH during hypoglycemia (2) that occurs in response to the decrease in VMH glucose (10).…”

mentioning

confidence: 99%

Rate of fall in blood glucose and recurrent hypoglycemia affect glucose dynamics and noradrenergic activation in the ventromedial hypothalamus

Barnes¹,

Lawson

Beverly

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Noradrenergic activity in the ventromedial hypothalamus (VMH) is increased and activates a sympathoadrenal response during hypoglycemia. How the rate at which hypoglycemia develops affects local glucose concentrations and norepinephrine (NE) release was evaluated by placing microdialysis probes into the VMH of male Sprague-Dawley rats receiving insulin (20 mU·kg(-1)·min(-1)) and variable glucose infusions. During a first episode of hypoglycemia, interstitial glucose concentrations in the VMH generally declined at the same rate as plasma glucose; however, the faster hypoglycemia developed, the greater the magnitude of the initial NE release in the VMH (r(2) = 0.72, P < 0.001). Following recurrent episodes of hypoglycemia, VMH glucose decreased at a slower rate than plasma glucose, and the initial NE release was attenuated at the same rates of blood glucose decline. The plasma glucose threshold for the initial NE release in VMH was similar for all groups (∼3.23 mM); however, the VMH glucose threshold was stimulated and was lower when blood glucose declined more slowly (0.86 ± 0.06 vs. 1.06 ± 0.04 mmol/l, P < 0.01). The timing of the initial increase in NE release in VMH corresponded with an increase in plasma epinephrine during the first episode of hypoglycemia but not following recurrent hypoglycemia. Although a decrease in VMH glucose concentration is required for noradrenergic activation in VMH, there does not appear to be a set glucose threshold within the VMH for activation of this response.

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Hypoglycemia-induced noradrenergic activation in the VMH is a result of decreased ambient glucose

Cited by 34 publications

References 33 publications

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device

Rate of fall in blood glucose and recurrent hypoglycemia affect glucose dynamics and noradrenergic activation in the ventromedial hypothalamus

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