Glucose and endocrine responses to hypothalamic electrical stimulation in rats

Dubuc, Paul U.; Leshin, L.S.; Willis, Patricia

doi:10.1152/ajpregu.1982.242.3.r220

Cited by 6 publications

(5 citation statements)

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“…Our findings that Ucn3/TRH axons densely innervate the VMN and constitute almost the entire TRH innervation and the total Ucn3 innervation of this nucleus strongly suggest that Ucn3/TRH neurons are involved in the regulation of feeding, as both TRH and Ucn3 decrease food intake and increase blood glucose levels when injected to the VMN (Suzuki et al,1982; Shen et al,1985; Fekete et al,2007; Li et al,2007). Since the electrical stimulation of the VMN inhibits feeding (Beltt and Keesey,1975; Ruffin and Nicolaidis,1999) and causes hyperglycemia (Dubuc et al,1982), these data indicate that Ucn3/TRH axons exert stimulatory effects on VMN neurons. Reducing food intake probably involves the stimulation of leptin‐sensitive neurons located in the dorsomedial part of the VMN (Elmquist et al,1997,1998), a region that also receives the highest density of Ucn3/TRH axons.…”

Section: Discussionmentioning

confidence: 94%

Surgical pathology stage by American Joint Commission on Cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma

Rohatgi

Mansfield

Crane

et al. 2006

Cancer

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The JAK2 V617F mutation is responsible for the constitutive activation of the erythropoietin receptor signaling pathway in most cases of polycythemia vera (PV). The mutation has also been described in healthy people. As smoking may result in secondary polycythemia, the goal of this trial was to examine the effect of smoking on the prevalence of the JAK2 mutation and its correlation to erythrocytosis. The study was case–control. Hospitalized smokers (n = 81) and nonsmokers (n = 61) were recruited. Serum was drawn for complete blood count, erythropoietin, ferritin and venous blood gases. JAK2 mutation was analyzed by highly sensitive allele‐specific Quantitative Real Time PCR. The JAK2 mutation was found in 29/81 (35.8%) of smokers in comparison to only 9/61 (14.8%) of the control group (P = 0.007). The frequency of the mutation among smokers who were positive for the JAK2 mutation had a mean of 6.78 × 10−4 ± 1.08 × 10−3 vs. 1.51 × 10−4 ± 2.04 × 10−4 among nonsmokers (P = 0.027). Both frequencies are much lower than those found in PV. There was a medium correlation between older age and mutation frequency in nonsmokers (r= 0.67, P = 0.043). Hematocrit was higher in smokers (47.8 ± 6 vs. 41.7 ± 4.7, P < 0.0001), but no correlation was found to JAK2 mutation. In a cohort of hospitalized smokers and nonsmokers, JAK2 mutation was more prevalent and found in higher frequencies among smokers than nonsmokers. We suggest that accelerated erythropoiesis renders the cells susceptible to JAK2 mutation. Am. J. Hematol., 2011. © 2011 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 94%

Surgical pathology stage by American Joint Commission on Cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma

Rohatgi

Mansfield

Crane

et al. 2006

Cancer

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“…From a teleological perspective, it makes intuitive sense that, when glucose availability is threatened, responses that increase glucose production would be activated (e.g., elevated glucagon and corticosterone levels) in concert with responses that reduce glucose clearance (e.g., inhibition of insulin secretion), and much of the literature indicates that pancreatic beta cells are subject to inhibitory control via the sympathetic nervous system (SNS) (47,48). For example, bilateral VMN lesioning induces hyperinsulinemia (49,50) whereas electrical stimulation of the VMN suppresses glucose-induced insulin secretion (51). Further, the VMN is known to regulate autonomic outflow to the pancreas (52,53), and activation of islet sympathetic nerves during glycopenic stress (54) inhibits insulin secretion via a mechanism involving activation of α2-adrenoreceptors on the beta cell (47,48).…”

Section: Discussionmentioning

confidence: 99%

Functional identification of a neurocircuit regulating blood glucose

Meek

Nelson

Matsen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

159

187

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Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMN SF1 neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMN SF1 neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMN SF1 fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMN SF1 neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMN SF1 neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMN SF1 neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN→VMN SF1 →aBNST neurocircuit.glucoregulatory circuit | counter regulation | ventromedial nucleus | bed nucleus of the stria terminalis | hyperglycemia B ecause the brain relies exclusively on glucose as a fuel source, brain function is rapidly compromised when circulating glucose levels drop below the normal range. Consequently, hypoglycemia elicits a robust, integrated, and redundant set of counterregulatory responses (CRRs) that ensure the rapid and efficient recovery of plasma glucose concentrations into the normal range (1). Components of the CRR include increased secretion of the hormones glucagon, epinephrine, and glucocorticoids, inhibition of glucoseinduced insulin secretion, increased sympathetic nervous system (SNS) outflow to the liver, and increased food intake (1-3). Owing to this redundancy, recovery from hypoglycemia is difficult to block in normal humans and animal models, even when adrenal or glucagon responses are prevented. Only when multiple responses are blocked is the ability to recover from hypoglycemia significantly compromised (4). This arrangement is perhaps unsurprising, given the threat to survival posed by hypoglycemia.Although glucose sensing can occur at peripheral (e.g., neurons innervating the hepatic portal vein) as well as central sites (3, 5), the brain is the organ responsible both for transducing this information into effective glucose counterregulation and for terminating this response once euglycemia is restored. Of the many brain areas that have been investigated, the hypothalamic ventromedial nucleus (VMN) has emerged as potentially being both necessary and sufficient to elicit this powerful response. This assertion is based on evidence that, whereas electrical stimulation of the VMN activates the CRR and thereby raises circulating glucose levels (6), glucose infusion directly into the VMN can suppress the CRR during hypoglycemia (7) and thereby impair recovery of normal blood glucose levels (8). Moreover, two recent papers identified a circuit comprise...

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“…Although glucose counterregulation involves multiple brain areas (1), neurons in the hypothalamic ventromedial nucleus (VMN) appear to play an important role. This assertion is based on evidence that 1 ) the VMN is activated during hypoglycemia (7), 2 ) electrical stimulation of the VMN activates CRRs and raises blood glucose levels (8,9), and 3 ) glucose delivery specifically within the VMN blunts CRRs during systemic hypoglycemia (10). Moreover, using an optogenetics approach, we recently demonstrated that activation of the subset of VMN neurons that express steroidogenic factor 1 (VMN SF1 neurons) activates CRRs and thereby raises blood glucose levels, whereas their inhibition blocks recovery from hypoglycemia (11).…”

Section: Introductionmentioning

confidence: 99%

Distinct Neuronal Projections From the Hypothalamic Ventromedial Nucleus Mediate Glycemic and Behavioral Effects

et al. 2018

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The hypothalamic ventromedial nucleus (VMN) is implicated both in autonomic control of blood glucose and in behaviors including fear and aggression, but whether these divergent effects involve the same or distinct neuronal subsets and their projections is unknown. To address this question, we used an optogenetic approach to selectively activate the subset of VMN neurons that express neuronal nitric oxide synthase 1 (VMNNOS1 neurons) implicated in glucose counterregulation. We found that photoactivation of these neurons elicits 1) robust hyperglycemia achieved by activation of counterregulatory responses usually reserved for the physiological response to hypoglycemia and 2) defensive immobility behavior. Moreover, we show that the glucagon, but not corticosterone, response to insulin-induced hypoglycemia is blunted by photoinhibition of the same neurons. To investigate the neurocircuitry by which VMNNOS1 neurons mediate these effects, and to determine whether these diverse effects are dissociable from one another, we activated downstream VMNNOS1 projections in either the anterior bed nucleus of the stria terminalis (aBNST) or the periaqueductal gray (PAG). Whereas glycemic responses are fully recapitulated by activation of VMNNOS1 projections to the aBNST, freezing immobility occurred only upon activation of VMNNOS1 terminals in the PAG. These findings support previous evidence of a VMN→aBNST neurocircuit involved in glucose counterregulation and demonstrate that activation of VMNNOS1 neuronal projections supplying the PAG robustly elicits defensive behaviors.

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Glucose and endocrine responses to hypothalamic electrical stimulation in rats

Cited by 6 publications

References 0 publications

Surgical pathology stage by American Joint Commission on Cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma

Surgical pathology stage by American Joint Commission on Cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma

Functional identification of a neurocircuit regulating blood glucose

Distinct Neuronal Projections From the Hypothalamic Ventromedial Nucleus Mediate Glycemic and Behavioral Effects

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