Immunocytochemical localization of the insulin-responsive glucose transporter 4 (Glut4) in the rat central nervous system

Messari, Saïd El; Leloup, Corinne; Quignon, Monique; Brisorgueil, Marie‐Jeanne; Pénicaud, Luc; Arluison, Michel

doi:10.1002/(sici)1096-9861(19981005)399:4<492::aid-cne4>3.0.co;2-x

Cited by 156 publications

(106 citation statements)

References 56 publications

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“…However, a recent re-evaluation by Knudsen et al (33) of the data from Hertz et al (1) suggested that insulin may not truly have an effect on glucose transport/metabolism in humans, a conclusion that is also supported by the report of Cranston et al (7). Interestingly, both insulin receptors (34 -36) and insulinsensitive GLUT4 (37)(38)(39)(40)(41) have been found at the bloodbrain barrier, and insulin has been shown to be an important modulator of the autonomic response to hypoglycemia (42) and of feeding behavior (43). Insulin crosses the blood-brain barrier via receptor-mediated transcytosis.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Insulin on In Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport/Metabolism in Humans

et al. 2001

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The continuous delivery of glucose to the brain is critically important to the maintenance of normal metabolic function. However, elucidation of the hormonal regulation of in vivo cerebral glucose metabolism in humans has been limited by the lack of direct, noninvasive methods with which to measure brain glucose. In this study, we sought to directly examine the effect of insulin on glucose concentrations and rates of glucose transport/metabolism in human brain using 1 H-magnetic resonance spectroscopy at 4 Tesla. Seven subjects participated in paired hyperglycemic (16.3 ؎ 0.3 mmol/l) clamp studies performed with and without insulin. Brain glucose remained constant throughout (5.3 ؎ 0.3 mol/g wet wt when serum insulin ‫؍‬ 16 ؎ 7 pmol/l vs. 5.5 ؎ 0.3 mol/g wet wt when serum insulin ‫؍‬ 668 ؎ 81 pmol/l, P ‫؍‬ NS). Glucose concentrations in gray matter-rich occipital cortex and white matter-rich periventricular tissue were then simultaneously measured in clamps, where plasma glucose ranged from 4.4 to 24.5 mmol/l and insulin was infused at 0.5 mU ⅐ kg -1 ⅐ min -1 . The relationship between plasma and brain glucose was linear in both regions. Reversible Michaelis-Menten kinetics fit these data best, and no differences were found in the kinetic constants calculated for each region. These data support the hypothesis that the majority of cerebral glucose uptake/metabolism is an insulin-independent process in humans. Diabetes 50: [2203][2204][2205][2206][2207][2208][2209] 2001 T he brain relies on the continuous delivery of glucose via the blood to maintain normal metabolic function. How glucose delivery into the central nervous system is regulated and how that delivery is altered by different metabolic conditions in the living human have been difficult to ascertain. In particular, the role of insulin in the regulation of cerebral glucose metabolism has been difficult to directly assess. Although evidence acquired using both in vitro and in vivo approaches support and refute the hypothesis that insulin regulates the entry of glucose into brain tissue (1-9), studies performed in living animals have been limited by their inability to directly measure cerebral glucose concentrations.The brain is composed of both gray and white matter. Both rely on glucose for the maintenance of normal function, but the rates at which they metabolize glucose have been found to be different (9,10). Whether these differences in glucose metabolism equate to differences in cerebral glucose concentrations and whether insulin differentially regulates regional cerebral glucose metabolism have not been directly examined in humans because, until recently, direct methods to measure brain glucose concentrations in healthy subjects have not been feasible. Invasive methods to measure intracerebral glucose concentrations, such as the use of an implanted equilibrium dialysis probe, have been reported in abstract form (11), but such a technique is not acceptable in the study of normal human physiology. Indirect methods to quantitate brain glucose concent...

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Section: Discussionmentioning

confidence: 99%

The Effect of Insulin on In Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport/Metabolism in Humans

et al. 2001

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“…For instance, the cerebellum expresses a high density of leptin receptors (Guan et al, 1997) whose expression is clearly downregulated by high-fat feeding (Koros et al, 2009), suggesting that peripheral leptin could well transmit metabolic signals to that structure. Another example is the expression of glucose transporters (Glut), including the insulinresponsive Glut4, in the cerebellum (El Messari et al, 1998;Choeiri et al, 2002), suggesting that glucose and/or insulin could provide afferent signals to that brain region.…”

Section: Afferent Pathways Conveying Nutritional Cues To the Cerebellmentioning

confidence: 99%

The Cerebellum Harbors a Circadian Oscillator Involved in Food Anticipation

Mendoza¹,

Pévet²,

et al. 2010

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The cerebellum participates in motor coordination as well as in numerous cerebral processes, including temporal discrimination. Animals can predict daily timing of food availability, as manifested by food-anticipatory activity under restricted feeding. By studying ex vivo clock gene expression by in situ hybridization and recording in vitro Per1-luciferase bioluminescence, we report that the cerebellum contains a circadian oscillator sensitive to feeding cues (i.e., whose clock gene oscillations are shifted in response to restricted feeding). Food-anticipatory activity was markedly reduced in mice injected intracerebroventricularly with an immunotoxin that depletes Purkinje cells (i.e., OX7-saporin). Mice bearing the hotfoot mutation (i.e., Grid2 ho/ho ) have impaired cerebellar circuitry and mild ataxic phenotype. Grid2 ho/ho mice fed ad libitum showed regular behavioral rhythms and day-night variations of clock gene expression in the hypothalamus and cerebellum. When challenged with restricted feeding, however, Grid2 ho/ho mice did not show any food-anticipatory rhythms, nor timed feeding-induced changes in cerebellar clock gene expression. In hypothalamic arcuate and dorsomedial nuclei, however, shifts in Per1 expression in response to restricted feeding were similar in cerebellar mutant and wild-type mice. Furthermore, plasma corticosterone and metabolites before mealtime did not differ between cerebellar mutant and wild-type mice. Together, these data define a role for the cerebellum in the circadian timing network and indicate that the cerebellar oscillator is required for anticipation of mealtime.

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“…The other was the hippocampal formation (HF; consisting of hippocampus fields CA1-CA3, the dentate gyrus, and the subiculum), which develops marked pathology starting early in the disorder (61,63). Both these brain areas express the IR and IGF-1R (64,65), as well as insulin-sensitive GLUT4 (66)(67)(68)(69)(70). We then focused on the HF to study the causes and consequences of brain insulin resistance, since it is more directly involved in AD pathogenesis (61,63) and cognitive decline (71,72).…”

Section: Introductionmentioning

confidence: 99%

Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline

Talbot¹,

Wang²,

Kazi³

et al. 2012

J. Clin. Invest.

1,522

1,338

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Immunocytochemical localization of the insulin-responsive glucose transporter 4 (Glut4) in the rat central nervous system

Cited by 156 publications

References 56 publications

The Effect of Insulin on In Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport/Metabolism in Humans

The Effect of Insulin on In Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport/Metabolism in Humans

The Cerebellum Harbors a Circadian Oscillator Involved in Food Anticipation

Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline

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