Electrophysiological properties and glucose responsiveness of guinea‐pig ventromedial hypothalamic neurones in vitro.

Minami, Taketsugu; Osuga, Yutaka; Sugimori, Mutsuyuki

doi:10.1113/jphysiol.1986.sp016276

Cited by 84 publications

(58 citation statements)

References 40 publications

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“…Again, in the absence of GLUT2, there is a lack of glucose sensing and therefore a lack of inhibition of the autonomic tone. Although this interpretation requires direct experimental verification, we believe that it is compatible with the glucose sensitivity of neurons found in the hypothalamus, which can respond to low-or high-glucose concentrations by increasing or decreasing their firing rates (17)(18)(19)(20)(21). For example, the majority of glucose-sensitive neurons of the lateral hypothalamic area decreased their firing rates in response to small increases in local glucose concentrations.…”

Section: Glut2 and Regulated Glucacon Secretionsupporting

confidence: 68%

“…The mechanisms by which these centers become activated by changes in glycemic levels are not completely understood at the molecular level. It has however been described that glucose-sensitive neurons are present in these different parts of the hypothalamus (17)(18)(19)(20)(21). These neurons respond to low-or high-glucose concentrations either by increasing or decreasing their firing rates.…”

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confidence: 99%

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Evidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion

Burcelin

Thorens

2001

Diabetes

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GLUT2؊/؊ mice reexpressing GLUT1 or GLUT2 in their ␤-cells (RIPGLUT1 ؋ GLUT2 ؊/؊ or RIPGLUT2 ؋ GLUT2 ؊/؊ mice) have nearly normal glucose-stimulated insulin secretion but show high glucagonemia in the fed state. Because this suggested impaired control of glucagon secretion, we set out to directly evaluate the control of glucagonemia by variations in blood glucose concentrations. Using fasted RIPGLUT1 ؋ GLUT2 ؊/؊ mice, we showed that glucagonemia was no longer increased by hypoglycemic (2.5 mmol/l glucose) clamps or suppressed by hyperglycemic (10 and 20 mmol/l glucose) clamps. However, an increase in plasma glucagon levels was detected when glycemia was decreased to <1 mmol/l, indicating preserved glucagon secretory ability, but of reduced sensitivity to glucopenia. To evaluate whether the high-fed glucagonemia could be due to an abnormally increased tone of the autonomic nervous system, fed mutant mice were injected with the ganglionic blockers hexamethonium and chlorisondamine. Both drugs lead to a rapid return of glucagonemia to the levels found in control fed mice. We conclude that 1) in the absence of GLUT2, there is an impaired control of glucagon secretion by low or high glucose; 2) this impaired glucagon secretory activity cannot be due to absence of GLUT2 from ␣-cells because these cells do not normally express this transporter; 3) this dysregulation may be due to inactivation of GLUT2-dependent glucose sensors located outside the endocrine pancreas and controlling glucagon secretion; and 4) because fed hyperglucagonemia is rapidly reversed by ganglionic blockers, this suggests that in the absence of GLUT2, there is an increased activity of the autonomic nervous system stimulating glucagon secretion during the fed state.

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Section: Glut2 and Regulated Glucacon Secretionsupporting

confidence: 68%

mentioning

confidence: 99%

Evidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion

Burcelin

Thorens

2001

Diabetes

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“…4C1). A similar phenomenon was observed in one type of glucoseresponsive neurons in guinea pig VMH (Minami et al 1986). The LTS was calcium dependent because it persisted in the presence of TTX (0.5 M) but was blocked by nickel (200 M) (n ϭ 4) (Fig.…”

Section: Membrane Properties Of Vglut2 Cells In Vmhsupporting

confidence: 51%

“…The mean input resistance was 591 Ϯ 26 M⍀ (range, 320 -1280 M⍀; n ϭ 48) calculated from the linear part of the slope of the current-voltage relationship between Ϫ60 and 0 mV (Fig. 4C1,C2), which is higher than that of general VMH neurons measured using intracellular recording (Minami et al, 1986;Priestley, 1992). In 13 of 23 cells, outward current injections into cells that were hyperpolarized negative to Ϫ70 mV generated a low-threshold spike (LTS) on which one or more fast spikes rode (Fig.…”

Section: Membrane Properties Of Vglut2 Cells In Vmhmentioning

confidence: 78%

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Pol²

2008

J. Neurosci.

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Anorexigenic melanocortins decrease food intake by activating MC3/MC4 receptors (MC3/4R); the prevailing view is that the orexigenic neuropeptide agouti-related peptide (AgRP) exerts the opposite action by acting as an antagonist at MC3/MC4 receptors. A total of 370 hypothalamic ventromedial nucleus (VMH) glutamatergic neurons was studied using whole-cell recording in hypothalamic slices from a novel mouse expressing green fluorescent protein (GFP) under control of the vesicular glutamate transporter 2 (vGluT2) promoter. Massive numbers of GFP-expressing VMH dendrites extended out of the core of the nucleus into the surrounding cell-poor shell. VMH dendrites received frequent appositions from AgRP-immunoreactive axons in the shell of the nucleus, but not the core, suggesting that AgRP may influence target VMH neurons. ␣-MSH, melanotan II (MTII), and selective MC3R or MC4R agonists were all inhibitory, reducing the spontaneous firing rate and hyperpolarizing vGluT2 neurons. The MC3/4R antagonist SHU9119 was excitatory. Unexpectedly, AgRP did not attenuate MTII actions on these neurons; instead, these two compounds showed an additive inhibitory effect. In the absence of synaptic activity, no hyperpolarization or change in input resistance was evoked by either MTII or AgRP, suggesting indirect actions. Consistent with this view, MTII increased the frequency of spontaneous and miniature IPSCs. In contrast, the mechanism of AgRP inhibition was dependent on presynaptic inhibition of EPSCs mediated by G i /G o -proteins, and was attenuated by pertussis toxin and NF023, inconsistent with mediation by G s -proteins associated with MC receptors. Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors.

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“…Both IA current and after hyperpolarization tended to reduce the firing rate. The non GR neurons fired at a higher rate, and exhibited interneuron properties [20].…”

Section: Chemical Sensingmentioning

confidence: 99%

Feeding control through bioassay of body chemistry.

Osuga¹

1985

Jpn.J.Physiol

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Organisms function, in part, through processes of continuous assay of chemical conditions in the body. The body's ability to do this is evident from the many examples of bioassay that have been used since the earliest studies of biology. Some monitoring systems in the body respond rather specifically to individual factors, while others are dedicated to control of specialized mechanisms that are essential to survival. Evidence obtained from lesions produced in various sites within the hypothalamus led to early conclusions that feeding behavior was controlled or could at least be modified within that general region. There was, of course, controversy as to whether this was due to specific control centers or to fibers of passage through the hypothalamus. MORGANE [24] found that lesions of the lateral hypothalamic area (LHA) at the level of the ventromedial hypothalamic nucleus (VMH) did, in fact, greatly affect feeding behavior, while rostral or caudal lesions did not. This gave credence to the idea of control from a center, but still the controversy continued. Later GROSSMAN and GROSSMAN [6], with their kainic acid technique, managed to lesion neurons while leaving fibers of passage intact. This further supported the control center idea. More direct evidence in support of control centers has accumulated from micro injections, either directly or intracerebroventricularly, from electrophysiology and from electrophoretic drug applications. At present, widely distributed networks are known, and these certainly involve some rather extensive pathways. However, the networks join centers that lie not just in the nervous system, but in other organs as well, especially the viceral organs. With techniques now available it has been shown, without doubt, both directly and by deductive methods, that feeding can be, and probably is, controlled from several discrete centers. Some of this proof will be presented in this review which discusses progress in the study of neuronal and behavioral responses to body fluid factors and their consequent control of the feeding process. NEURONAL NETWORKS INVOLVED IN FEEDINGImportant information relevant to the regulation of feeding goes to the hypo-

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Electrophysiological properties and glucose responsiveness of guinea‐pig ventromedial hypothalamic neurones in vitro.

Cited by 84 publications

References 40 publications

Evidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion

Evidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Feeding control through bioassay of body chemistry.

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