Sensitivity of nucleus tractus solitarius neurons to induced moderate hyperglycemia, with special reference to catecholaminergic regions

Yettefti, Khadija; Orsini, J.C.; Ouazzani, T. El; Himmi, T.; Boyer, A.; Perrin, J.

doi:10.1016/0165-1838(94)00130-c

Cited by 60 publications

(33 citation statements)

References 23 publications

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“…The ability of glucose to alter the activity of brain stem neurons has been well documented; NTS neurons respond to glucose with either a decrease in activity (glucose-sensitive or glucose-inhibited neurons) or an increase in activity (glucose-responsive or glucose-excited neurons) (1,13,14,32,55,56). Thus NTS neurons appear to differ from other central nuclei where generally either only glucose-inhibited neurons or only glucose-excited neurons were identified, e.g., lateral hypothalamus or ventromedial hypothalamus and arcuate nucleus, respectively (19,34,39).…”

Section: Discussionmentioning

confidence: 99%

d-Glucose modulates synaptic transmission from the central terminals of vagal afferent fibers

Wan¹,

Browning²

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Wan S, Browning KN. D-Glucose modulates synaptic transmission from the central terminals of vagal afferent fibers. Am J Physiol Gastrointest Liver Physiol 294: G757-G763, 2008. First published January 17, 2008 doi:10.1152/ajpgi.00576.2007.-Experimental evidence suggests that glucose modulates gastric functions via vagally mediated effects. It is unclear whether glucose affects only peripheral vagal nerve activity or whether glucose also modulates vagal circuitry at the level of the brain stem. This study used whole cell patch-clamp recordings from neurons of the nucleus of the tractus solitarius (NTS) to assess whether acute variations in glucose modulates vagal brain stem neurocircuitry. Increasing D-glucose concentration induced a postsynaptic response in 40% of neurons; neither the response type (inward vs. outward current) nor response magnitude was altered in the presence of tetrodotoxin suggesting direct effects on the NTS neuronal membrane. In contrast, reducing D-glucose concentration induced a postsynaptic response (inward or outward current) in 54% of NTS neurons; tetrodotoxin abolished these responses, suggesting indirect sites of action. The frequency, but not amplitude, of spontaneous and miniature excitatory postsynaptic currents (EPSCs) was correlated with D-glucose concentration in 79% of neurons tested (n ϭ 48). Prior surgical afferent rhizotomy abolished the ability of D-glucose to modulate spontaneous EPSC frequency, suggesting presynaptic actions at vagal afferent nerve terminals to modulate glutamatergic synaptic transmission. In experiments in which EPSCs were evoked via electrical stimulation of the tractus solitarius, EPSC amplitude correlated with D-glucose concentration. These effects were not mimicked by L-glucose, suggesting the involvement of glucose metabolism, not uptake, in the nerve terminal. These data suggest that the synaptic connections between vagal afferent nerve terminals and NTS neurons are a strong candidate for consideration as one of the sites where glucose-evoked changes in vagovagal reflexes occurs. brain stem; electrophysiology; vagus DELAYED GASTRIC EMPTYING, or gastroparesis (diabetic gastropathy) in its extreme state, is reported in ϳ35-50% of patients with Type 1 or Type 2 diabetes (17,25,44,52) and is associated with early satiety, nausea, vomiting, and abdominal pain. Autonomic nerve dysfunction(s) undoubtedly contribute to the development of this syndrome (52), but reports that physiological hyperglycemia delays gastric emptying have led to the understanding that poor glycemic control per se may be responsible for at least some of these symptoms (25,26,37,38,45). Acute changes in blood glucose concentration, even within the physiological range, have profound effects on gastrointestinal functions, including gastric emptying. In healthy subjects, gastric emptying of both solids and liquids is slower at a blood glucose concentration of 8 mM than at 4 mM, and profound hyperglycemia (15 mM) causes a clear relaxation of the proximal stomach (29, 37). Hypoglycemia,...

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Section: Discussionmentioning

confidence: 99%

d-Glucose modulates synaptic transmission from the central terminals of vagal afferent fibers

Wan¹,

Browning²

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…To determine an index for the individual tissue glucose utilization rate, a flash injection of 1 µCi per gram of mouse of 14 C-2-deoxyglucose ( 14 C-2DG) (NEN LifeScience) through the femoral vein was performed 60 min before the end of the infusions (27,(29)(30)(31). Plasma 14 C-2DG disappearance was determined in 5-µl drops of blood sampled from the tip of the tail vein at 0, 5,10,15,20,25,30,45, and 60 min after the injection (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…He suggested that the brain was able to sense hypoglycemia and trigger a counterregulatory response. More recently, glucose-sensitive neuronal elements have been found in the lateral and ventromedial hypothalamic nuclei (2,3), the nucleus of the solitary tract (4,5), and autonomic afferent nerves originating from visceral organs, such as the liver and the gastrointestinal tract (6)(7)(8)(9). In particular, a glucose sensor has been localized in the portal vein upstream of the hepatic hilus (10).…”

Section: Rémy Burcelin Wanda Dolci and Bernard Thorensmentioning

confidence: 99%

Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization.

2000

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To analyze the role of the murine hepatoportal glucose sensor in the control of whole-body glucose metabolism, we infused glucose at a rate corresponding to the endogenous glucose production rate through the portal vein of conscious mice (Po-mice) that were fasted for 6 h. Mice infused with glucose at the same rate through the femoral vein (Fe-mice) and mice infused with a saline solution (Sal-mice) were used as controls. In Po-mice, hypoglycemia progressively developed until glucose levels dropped to a nadir of 2.3 ± 0.1 mmol/l, whereas in Fe-mice, glycemia rapidly and transiently developed, and glucose levels increased to 7.7 ± 0.6 mmol/l before progressively returning to fasting glycemic levels. Plasma insulin levels were similar in both Po-and Fe-mice during and at the end of the infusion periods (21.2 ± 2.2 vs. 25.7 ± 0.9 µU/ml, respectively, at 180 min of infusion). The whole-body glucose turnover rate was significantly higher in Po-mice than in Fe-mice (45.9 ± 3.8 vs. 37.7 ± 2.0 mg · kg -1 · min -1 , respectively) and in Sal-mice (24.4 ± 1.8 mg · kg -1 · min -1 ). Somatostatin co-infusion with glucose in Po-mice prevented hypoglycemia without modifying the plasma insulin profile. Finally, tissue glucose clearance, which was determined after injecting 14 C-2-deoxyglucose, increased to a higher level in Po-mice versus Fe-mice in the heart, brown adipose tissue, and the soleus muscle. Our data show that stimulation of the hepatoportal glucose sensor induced hypoglycemia and increased glucose utilization by a combination of insulin-dependent and insulin-independent or -sensitizing mechanisms. Furthermore, activation of the glucose sensor and/or transmission of its signal to target tissues can be blocked by somatostatin. Diabetes 49:1635-1642, 2000

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“…These neurons respond to low-or high-glucose concentrations either by increasing or decreasing their firing rates. Their activity may also be influenced by glucose-sensitive neurons of the nucleus of the tractus solitarius, which are directly sensitive to glycemic variations and send projections toward the lateral hypothalamus and paraventricular nucleus (20,(22)(23)(24)(25). It has been demonstrated that glucose-sensitive neurons of the brainstem participate in the response of the ANS to hypoglycemia in the dog by showing that counterregulation could be partially suppressed by maintaining normoglycemia specifically in the brainstem (26).…”

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confidence: 99%

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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Sensitivity of nucleus tractus solitarius neurons to induced moderate hyperglycemia, with special reference to catecholaminergic regions

Cited by 60 publications

References 23 publications

d-Glucose modulates synaptic transmission from the central terminals of vagal afferent fibers

d-Glucose modulates synaptic transmission from the central terminals of vagal afferent fibers

Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization.

Evidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion

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