Subgroups of hindbrain catecholamine neurons are selectively activated by 2-deoxy-d-glucose induced metabolic challenge

Ritter, Sue; Llewellyn‐Smith, Ida J.; Dinh, Thu

doi:10.1016/s0006-8993(98)00655-6

Cited by 183 publications

(179 citation statements)

References 60 publications

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“…Supporting this, local PVH or systemically delivered 2-DG trigger NE release in the PVH vicinity (McCaleb and Myers, 1982;Peinado and Myers, 1987;Nagatani et al, 1996). Importantly, however, this conclusion applies equally to epinephrine (E), because both NE injection and E activate identical receptors, and the critical CA afferents also contain E. Moreover, 2-DG preferentially triggers Fos expression in hindbrain E neurons, well known to project to the PVH (Ritter et al, 1998).…”

Section: Pvh-injected Ne Recapitulates Neuroendocrine Responses To Glmentioning

confidence: 91%

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

Khan¹,

Ponzio²,

Sanchez‐Watts³

et al. 2007

J. Neurosci.

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We show that systemic insulin and 2-DG, and PVH-targeted NE microinjections, rapidly elevated PVH phospho-ERK1/2 levels. NE increased Crh and c-fos expression, together with circulating ACTH/corticosterone. However, because injections also increased c-Fos mRNA in other brain regions, we used hypothalamic slices maintained in vitro to clarify whether NE activates PVH neurons without contribution of inputs from distal regions. In slices, bath-applied NE triggered robust phospho-ERK1/2 immunoreactivity in PVH (including CRH) neurons, which attenuated markedly in the presence of the ␣ 1 adrenoceptor antagonist, prazosin, or the MAP kinase kinase (MEK) inhibitor, U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene). Therefore, at a systems level, local PVH delivery of NE is sufficient to account for hindbrain activation of CRH neuroendocrine neurons during glycemic challenge. At a cellular level, these data provide the first demonstration that MAP kinase signaling cascades (MEK3 ERK) are intracellular transducers of noradrenergic signals in CRH neurons, and implicate this transduction mechanism as an important component of central neuroendocrine responses during glycemic challenge.

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Section: Pvh-injected Ne Recapitulates Neuroendocrine Responses To Glmentioning

confidence: 91%

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

Khan¹,

Ponzio²,

Sanchez‐Watts³

et al. 2007

J. Neurosci.

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“…[54][55][56] Also, in decerebrated rats, the hyperglycemic response to an intraperitoneal injection of 2-DG is preserved, 57 and c-fos immunostaining revealed that the activated neurons are present in the NTS, the dorsal motor nucleus of the vagus and the catecholaminergic neurons of the basolateral medulla. 58 Thus, hypoglycemia can be detected at several sites, the hepatoportal vein area, the brainstem and the hypothalamus. Although not discussed here, there is evidence that glomus cells in the carotid body are also activated by hypoglycemia and may contribute to the overall control of counter-regulation.…”

Section: S64mentioning

confidence: 99%

“…Furthermore, food intake can be stimulated by direct injections of 5-thio-glucose into the basolateral medulla, the dorsal motor nucleus of the vagus and the NTS, 54 where glucose-sensitive catecholaminergic neurons are located, which project to the hypothalamus, in particular the PVN and the AN. 55,58 Immunotoxin destruction of these neurons showed their role in the feeding response to the 2-DG glucoprivic signal 56 and in the regulation of NPY and Agrp expression. 55 A role for central Glut2 expression in feeding regulation has been suggested by experiments in which its expression was decreased by the injection of antisense oligonucleotides in the AN.…”

Section: Feeding Controlmentioning

confidence: 99%

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Thorens

2008

Int J Obes

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The control of body weight and of blood glucose concentrations depends on the exquisite coordination of the function of several organs and tissues, in particular the liver, muscle and fat. These organs and tissues have major roles in the use and storage of nutrients in the form of glycogen or triglycerides and in the release of glucose or free fatty acids into the blood, in periods of metabolic needs. These mechanisms are tightly regulated by hormonal and nervous signals, which are generated by specialized cells that detect variations in blood glucose or lipid concentrations. The hormones insulin and glucagon not only regulate glycemic levels through their action on these organs and the sympathetic and parasympathetic branches of the autonomic nervous system, which are activated by glucose or lipid sensors, but also modulate pancreatic hormone secretion and liver, muscle and fat glucose and lipid metabolism. Other signaling molecules, such as the adipocyte hormones leptin and adiponectin, have circulating plasma concentrations that reflect the level of fat stored in adipocytes. These signals are integrated at the level of the hypothalamus by the melanocortin pathway, which produces orexigenic and anorexigenic neuropeptides to control feeding behavior, energy expenditure and glucose homeostasis. Work from several laboratories, including ours, has explored the physiological role of glucose as a signal that regulates these homeostatic processes and has tested the hypothesis that the mechanism of glucose sensing that controls insulin secretion by the pancreatic beta-cells is also used by other cell types. I discuss here evidence for these mechanisms, how they integrate signals from other nutrients such as lipids and how their deregulation may initiate metabolic diseases.

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“…Hypoglycemia detection is thought to occur in specialized glucosesensing neurons within the portal venous system (3-5) and brain (6 -10), with the brain probably playing a predominant role. Within the brain, neurons whose activity appears to be directly linked to fluctuations in the glucose concentration to which they are exposed have been localized to the ventromedial hypothalamus (11) and to the brain stem (12,13). The mechanisms by which these systems are able to detect a falling glucose remain largely unknown.…”

mentioning

confidence: 99%

“…AMP-activated protein kinase (AMPK) is a serine/threonine kinase that has been proposed to function as an intracelullar fuel gauge (12,13,15). Activation of AMPK follows a rise in AMP concentration, as well as phosphorylation by a kinase kinase (AMPK kinase) (16).…”

mentioning

confidence: 99%

Potential Role for AMP-Activated Protein Kinase in Hypoglycemia Sensing in the Ventromedial Hypothalamus

et al. 2004

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The mechanisms by which specialized glucose-sensing neurons within the hypothalamus are able to detect a falling blood glucose remain largely unknown but may be linked to some gauge of neuronal energy status. We sought to test the hypothesis that AMP-activated protein kinase (AMPK), an intracellular kinase purported to act as a fuel sensor, plays a role in hypoglycemia sensing in the ventromedial hypothalamus (VMH) of the Sprague-Dawley rat by chemically activating AMPK in vivo through bilateral microinjection, before performing hyperinsulinemic-hypoglycemic or hyperinsulinemic-euglycemic clamp studies. In a subgroup of rats, H3-glucose was infused to determine glucose kinetics. The additional chemical activation by AICAR of AMPK in the VMH during hypoglycemia markedly reduced the amount of exogenous glucose required to maintain plasma glucose during hypoglycemia, an effect that was almost completely accounted for by a three-to fourfold increase in hepatic glucose production in comparison to controls. In contrast, no differences were seen between groups in hypoglycemia-induced rises in the principal counterregulatory hormones. In conclusion, activation of AMPK within the VMH may play an important role in hypoglycemia sensing. The combination of hypoglycemiaand AICAR-induced AMPK activity appears to result in a marked stimulus to hepatic glucose counterregulation.

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Subgroups of hindbrain catecholamine neurons are selectively activated by 2-deoxy-d-glucose induced metabolic challenge

Cited by 183 publications

References 60 publications

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Potential Role for AMP-Activated Protein Kinase in Hypoglycemia Sensing in the Ventromedial Hypothalamus

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