Glucose and Osmosensitive Neurones of the Rat Hypothalamus

Osuga, Yutaka; Ono, Takeshi; Ooyama, Hiroshi; Wayner, M.J.

doi:10.1038/222282a0

Cited by 568 publications

(328 citation statements)

References 6 publications

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“…Oomura and colleagues (137,138) showed that parenchymal application of glucose alters the activity of lateral and ventromedial hypothalamic neurons. These investigators extended their analyses to include caudal brainstem substrates, and showed that NTS neurons also displayed similar responses (63,124) and that the percentage of medullary neurons with these response profiles (20 -40%) was similar to that seen in hypothalamus.…”

Section: Glucose Sensorsmentioning

confidence: 99%

The Neuroanatomical Axis for Control of Energy Balance

Grill

Kaplan

2002

Frontiers in Neuroendocrinology

352

219

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The hypothalamic feeding-center model, articulated in the 1950s, held that the hypothalamus contains the interoceptors sensitive to blood-borne correlates of available or stored fuels as well as the integrative substrates that process metabolic and visceral afferent signals and issue commands to brainstem mechanisms for the production of ingestive behavior. A number of findings reviewed here, however, indicate that sensory and integrative functions are distributed across a central control axis that includes critical substrates in the basal forebrain as well as in the caudal brainstem. First, the interoceptors relevant to energy balance are distributed more widely than had been previously thought, with a prominent brainstem complement of leptin and insulin receptors, glucose-sensing mechanisms, and neuropeptide mediators. The physiological relevance of this multiple representation is suggested by the demonstration that similar behavioral effects can be obtained independently by stimulation of respective forebrain and brainstem subpopulations of the same receptor types (e.g., leptin, CRH, and melanocortin). The classical hypothalamic model is also challenged by the integrative achievements of the chronically maintained, supracollicular decerebrate rat. Decerebrate and neurologically intact rats show similar discriminative responses to taste stimuli and are similarly sensitive to intake-inhibitory feedback from the gut. Thus, the caudal brainstem, in neural isolation from forebrain influence, is sufficient to mediate ingestive responses to a range of visceral afferent signals. The decerebrate rat, however, does not show a hyperphagic response to food deprivation, suggesting that interactions between forebrain and brainstem are necessary for the behavioral response to systemic/ metabolic correlates of deprivation in the neurologically intact rat. At the same time, however, there is evidence suggesting that hypothalamic-neuroendocrine responses to fasting depend on pathways ascending from brainstem. Results reviewed are consistent with a distributionist (as opposed to hierarchical) model for the control of energy balance that emphasizes: (i) control mechanisms endemic to hypothalamus and brainstem that drive their unique effector systems on the basis of local interoceptive, and in the brainstem case, visceral, afferent inputs and (ii) a set of uni-and bidirectional interactions that coordinate adaptive neuroendocrine, autonomic, and behavioral responses to changes in metabolic status. KEY WORDS: feeding behavior; leptin; glucose sensing; decerebrate; neuropeptide; hypothalamic model; caudal brainstem; energy balance.

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Section: Glucose Sensorsmentioning

confidence: 99%

The Neuroanatomical Axis for Control of Energy Balance

Grill

Kaplan

2002

Frontiers in Neuroendocrinology

352

219

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“…Glucose-excited (GE) neurons increase, whereas glucose-inhibited (GI) neurons decrease their firing rate as ambient glucose levels rise (2)(3)(4). Although these neurons can respond directly or indirectly to either the complete absence of glucose or to levels as high as 20 mmol/l (2,(5)(6)(7)(8)(9), it is likely that their primary range is 0.5-3.5 mmol/l glucose under physiological conditions (4,10 -12). As in the pancreatic ␤-cell (13), the ATP-sensitive K ϩ (K ATP ) channel is an important component of glucosensing in GE neurons (3,5,14).…”

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confidence: 99%

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

et al. 2004

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To evaluate potential mechanisms for neuronal glucosensing, fura-2 Ca 2؉ imaging and single-cell RT-PCR were carried out in dissociated ventromedial hypothalamic nucleus (VMN) neurons. Glucose-excited (GE) neurons increased and glucose-inhibited (GI) neurons decreased intracellular Ca 2؉ ([Ca 2؉ ] i ) oscillations as glucose increased from 0.5 to 2.5 mmol/l. The Kir6.2 subunit mRNA of the ATP-sensitive K ؉ channel was expressed in 42% of GE and GI neurons, but only 15% of nonglucosensing (NG) neurons. Glucokinase (GK), the putative glucosensing gatekeeper, was expressed in 64% of GE, 43% of GI, but only 8% of NG neurons and the GK inhibitor alloxan altered [Ca 2؉ ] i oscillations in ϳ75% of GK-expressing GE and GI neurons. Insulin receptor and GLUT4 mRNAs were coexpressed in 75% of GE, 60% of GI, and 40% of NG neurons, although there were no statistically significant intergroup differences. Hexokinase-I, GLUT3, and lactate dehydrogenase-A and -B were ubiquitous, whereas GLUT2, monocarboxylate transporters-1 and -2, and leptin receptor and GAD mRNAs were expressed less frequently and without apparent relationship to glucosensing capacity. Thus, although GK may mediate glucosensing in up to 60% of VMN neurons, other regulatory mechanisms are likely to control glucosensing in the remaining ones. Diabetes 53:549 -559, 2004

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“…Here we focus on their role(s) in glucose homeostasis, particularly in the hypothalamus. Early electrophysiological studies identified a reciprocal response of hypothalamic neurons to applied glucose [3,111,112]. In the ventromedial hypothalamus (VMH), a majority of responding neurons increased their firing rate (glucose-responsive or glucose-stimulated), whereas in the lateral hypothalamus (LH), a majority reduced their activity (glucose-sensitive or glucose-inhibited).…”

Section: Acetylcholine and Amino Acidsmentioning

confidence: 99%

ABCC8 and ABCC9: ABC transporters that regulate K+ channels

Bryan

Muñoz

Zhang

et al. 2006

Pflugers Arch - Eur J Physiol

147

117

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The sulfonylurea receptors (SURs) ABCC8/ SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily. Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K + selective pores, either K IR 6.1/KCNJ8 or K IR 6.2/ KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K + channels found in endocrine cells, neurons, and both smooth and striated muscle. Adenine nucleotides, the major regulators of ATP-sensitive K + (K ATP ) channel activity, exert a dual action. Nucleotide binding to the pore reduces the activity or channel open probability, whereas Mg-nucleotide binding and/or hydrolysis in the nucleotidebinding domains of SUR antagonize this inhibitory action to stimulate channel openings. Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic β cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. Additionally, the subtle dysregulation of K ATP channel activity by a K IR 6.2 polymorphism has been suggested as a predisposing factor in type 2 diabetes mellitus. Studies on K ATP channel null mice are clarifying the roles of these metabolically sensitive channels in a variety of tissues.

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Glucose and Osmosensitive Neurones of the Rat Hypothalamus

Cited by 568 publications

References 6 publications

The Neuroanatomical Axis for Control of Energy Balance

The Neuroanatomical Axis for Control of Energy Balance

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

ABCC8 and ABCC9: ABC transporters that regulate K+ channels

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