Glucose Inhibition of the Glucose-sensitive Neurone in the Rat Lateral Hypothalamus

Osuga, Yutaka; Ooyama, Hiroshi; Sugimori, Mutsuyuki; Nakamura, Tsutomu; Yamada, Yasuyuki

doi:10.1038/247284a0

Cited by 350 publications

(181 citation statements)

References 14 publications

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“…High brain glucose concentrations suppress food intake and body mass consistent with a negative feedback regulation. 4,5 Pathways that allocate glucose into the brain, thereby increasing brain glucose feedback, should indirectly suppress food intake. 3 Vascular endothelial growth factor and sympathoadrenal activity may jointly contribute to such glucose allocation.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Increased brain glucose concentration is known to suppress food intake and thereby decrease body mass via action on hypothalamic regulation centers. 4,5 Blood glucose must be transported by carrier mechanisms across the blood-brain barrier (BBB) to become available for brain metabolism. The carrier protein specific for glucose transport across the BBB is the glucose transporter (GLUT) 1.…”

Section: Introductionmentioning

confidence: 99%

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High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes

et al. 2006

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Objective: Vascular endothelial growth factor (VEGF) has been suggested to enhance glucose transport across the blood-brain barrier, thereby increasing brain glucose supply. Increased brain glucose concentration is known to suppress food intake and to decrease body mass via action on hypothalamic regulation centers. Based on the crucial role of VEGF on brain glucose supply, we hypothesized that higher VEGF concentrations are associated with lower food intake and body mass in humans. Methods: Intending to investigate subjects with high variance of blood glucose, we examined patients with type 2 diabetes mellitus. Our hypothesis was tested in a population-based cohort of 190 subjects with type 2 diabetes. Plasma VEGF levels in conjunction with other parameters known to modulate food intake were measured and subsequently correlated with food intake patterns at a breakfast buffet as well as with body mass. Results: We found that subjects with higher concentrations of plasma VEGF had 17% less carbohydrate intake (P ¼ 0.003) and 4.8% lower body mass (P ¼ 0.017) than those with lower VEGF concentrations. Intake of protein and fat did not correlate with VEGF concentrations. These associations of plasma VEGF were confirmed in multiple linear regression analyses controlling for several parameters interacting with food intake. Conclusion: We conclude that high plasma VEGF concentrations are associated with less carbohydrate intake and lower body mass in type 2 diabetes. The role VEGF plays in facilitating glucose access to the brain represents a new aspect of food intake regulation and energy homeostasis, with relevance for diseases with body mass disturbances.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes

et al. 2006

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“…The inhibition of carnitine-palmitoyl transferase 1 (CPT-1) by malonyl-CoA subsequently leads to an increase in LCCoAs that can activate K ATP channels as illustrated in the lower right. Finally, early studies by Oomura and colleagues [113] implicated activation of the electrogenic sodium pump in the reduced firing rate of glucose-inhibited neurons. This hypothesis is supported by measurements of V m , [Na + ] i , and [K + ] i by Silver and Ereciñska [142], and the stimulation of pump activity by insulin via a multistep process involving insulin receptors (IRs) (reviewed in 146).…”

Section: Discussionmentioning

confidence: 99%

“…The metabolic control of firing rate in these neurons is poorly understood; three mechanisms, summarized schematically in Fig. 5, have been suggested: (1) Oomura and colleagues [113] proposed that increasing activity of the electrogenic sodium pump (Na + -/K + -ATPase), secondary to increased glucose metabolism, can hyperpolarize glucose-inhibited neurons. This would be consistent with the [Na + ] i and [K + ] i determinations of Silver and Erecińska [142] on glucose-inhibited neurons, and both insulin and long-chain acyl CoAs are reported to stimulate the sodium pump.…”

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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“…The portal signal can control food intake independent of catecholamines [41]. The lateral hypothalamus contains glucose-sensitive neurones that are stimulated by hypoglycaemia indirectly [47] via signals transmitted from the nucleus tractus solitarius [48]. The nucleus tractus solitarius receives input from vagal nerve afferents supplying the liver [49] and contains neurones that are stimulated by falling glucose [48] and inhibited by rising glucose in the portal circulation [50].…”

Section: Discussionmentioning

confidence: 99%

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man

et al. 2002

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Aims/hypothesis. The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers. Methods. Each subject received an insulin infusion (3 mU·kg -1 ·min -1 ) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp.Results. Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02±20.84 (means ± SD) to 15. vere hypoglycaemia during the pharmacological treatment of diabetes mellitus. The inability to generate or detect the warning symptoms of early hypoglycaemia puts diabetic patients at high risk of episodes of severe hypoglycaemia [1] and often the fear of hypoglycaemia limits the optimisation of glycaemic control [2]. Associated with loss of subjective awareness of hypoglycaemia is a lowering of the glucose concentration required to initiate the counterregulatory response to hypoglycaemia, as well as a reduction in the magnitude and intensity of the counterregulatory response at any given blood glucose concentration [3,4,5]. The speculation that these defects are principally the result of defective glucose sensing gains support from data showing similar changes in the neuroendocrine rePerception of a minor decrease in plasma glucose concentration and initiation of a counterregulatory response are essential factors in the defence against se-

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Glucose Inhibition of the Glucose-sensitive Neurone in the Rat Lateral Hypothalamus

Cited by 350 publications

References 14 publications

High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes

High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes

ABCC8 and ABCC9: ABC transporters that regulate K+ channels

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man

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