Discrete brain areas express the insulin-responsive glucose transporter GLUT4

Leloup, Corinne; Arluison, Michel; Kassis, Nadim; Lepetit, Nathalie; Cartier, Nathalie; Ferré, Pascal; Pénicaud, Luc

doi:10.1016/0169-328x(95)00306-d

Cited by 123 publications

(67 citation statements)

References 27 publications

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“…Insulin can be transported from plasma into brain through the blood brain barrier, achieving concentrations of about 3 pmol/l in the CNS [30,31]. The existence of insulin receptors [32,33] and GLUT-4, an insulin-sensitive glucose transporter [34,35,36], in the CNS supports the idea that insulin can exert direct actions in the CNS. Pre-incubation with insulin promotes survival of cultured neurons during glucose deprivation by facilitating glial glycogen synthesis [37].…”

Section: Discussionmentioning

confidence: 68%

Effects of insulin on long-term potentiation in hippocampal slices from diabetic rats

et al. 2003

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Aims/Hypothesis. Cognitive deficits occur commonly in diabetic patients. It is unclear whether these impairments result from hypoglycaemia during intensive insulin therapy, or from the diabetes itself. The aim of this study was to examine if impaired energy utilization resulting from insulin deficiency contributes to impaired long-term potentiation (reflecting impaired synaptic plasticity). As long-term potentiation is considered a candidate cellular mechanism underlying learning and memory, understanding how diabetes alters long-term potentiation may provide insight into mechanisms producing cognitive deficits in diabetes. Methods. Electrophysiologic recordings were used to study long-term potentiation in the CA1 region of hippocampal slices from healthy rats and rats with streptozotocin-induced diabetes.Results. Long-term potentiation was difficult to induce in slices from diabetic rats in standard recording buffer (contains 10 mmol/l glucose). In slices from diabetic rats, increasing extracellular glucose failed to recover long-term potentiation induction, but 10 mmol/l pyruvate added to standard buffer enabled long-term potentiation induction. Moreover, incubation of slices from diabetic rats with insulin enabled long-term potentiation induction in standard buffer. Acute administration of streptozotocin alone did not impair long-term potentiation in slices from healthy animals, and changing extracellular glucose concentrations over the range of 5 mmol/l to 30 mmol/l did not alter long-term potentiation in slices from control rats. Conclusions/interpretation. These observations suggest that impaired energy utilization from insulin deficiency, rather than the accompanying hyperglycaemia, impair long-term potentiation in diabetes. Impaired hippocampal synaptic plasticity could contribute to learning and cognitive impairment in diabetic patients. [Diabetologia (2003) Poor academic performance in diabetic children and memory impairment in adults with diabetes are viewed as increasing public health concerns. These problems are typically thought to result from hypoglycaemic attacks [1,2], which occur more frequently during intensive insulin therapy [3]. Although insulininduced hypoglycaemia could contribute to learning problems [4], one recent prospective study did not find a relationship between severe hypoglycaemic events and cognitive impairment [5], raising the possibility that the diabetic condition alone might adversely affect learning and memory. Experimental evidence supporting an independent effect of diabetes upon

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Section: Discussionmentioning

confidence: 68%

Effects of insulin on long-term potentiation in hippocampal slices from diabetic rats

et al. 2003

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“…GLUT1 can be readily detected in cultured neurons and is detected in vivo under conditions of stress such as following a hypoxic-ischemic insult (45,70,78,129,131). The presence of GLUT2 has been reported in neurons in the hypothalamus (7,8), and GLUT4 has been found in several subsets of neurons, including Purkinje and granule cells in cerebellum, principle and nonprinciple cells in the hippocampus, and isolated cells in the cortex and hypothalamus (5,7,12,67,72,106,126). Both GLUT6 and -8 have been reported to be present in neurons; however, as with GLUT4, both proteins contain a dileucine motif in their COOH termini and would appear to reside in intracellular membranes; GLUT8 may be recruited to the ER in the presence of insulin (see Ref.…”

Section: Neuronal Glut3 and Cerebral Glucose Utilizationmentioning

confidence: 99%

The facilitative glucose transporter GLUT3: 20 years of distinction

Simpson

Dwyer

Malide

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

395

322

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Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: [15245][15246][15247][15248] 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells.neurons; sperm; preimplantation embryo; white blood cells GLUCOSE METABOLISM IS VITAL to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3 which, as implied by its name, was the third glucose transporter to be cloned (62) and was originally designated as the neuronal glucose transporter. Together with GLUT1, -2, and -4, it comprises the Class 1 group of transporters (For review see Refs. 15,81,121). With the cloning of GLUT3, it became apparent that the brain did not rely exclusively on GLUT1 and that GLUT3 was highly and specifically expressed by neurons. Thus, GLUT3 became the third facilitative glucose transporter isoform with unique characteristics suited for cell-specific expression and function. GLUT2 is ideally suited for expression in liver and pancreas due to its high K m for glucose; GLUT4 and its translocation from intracellular vesicles to the cell surface facilitates insulin-stimulated glucose uptake in insulin-sensitive cells: muscle and fat. The overriding question that drove the early work in GLUT3 in the brain was: why would neurons need a separate glucose transporter isoform; what is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand?...

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“…Most neurons express primarily GLUT3, a high-capacity, low-K m transporter that is largely saturated at physiological brain glucose levels (35). On the other hand, the insulin-sensitive GLUT4 (36) is expressed in neurons and has a K m within the physiological range for brain glucose (36). Also, GLUT4 and insulin receptor (INS-R) expression overlap in brain areas involved in glucosensing (37) and thus might play a potential role in neuronal glucosensing.…”

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confidence: 99%

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

et al. 2004

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To evaluate potential mechanisms for neuronal glucosensing, fura-2 Ca 2؉ imaging and single-cell RT-PCR were carried out in dissociated ventromedial hypothalamic nucleus (VMN) neurons. Glucose-excited (GE) neurons increased and glucose-inhibited (GI) neurons decreased intracellular Ca 2؉ ([Ca 2؉ ] i ) oscillations as glucose increased from 0.5 to 2.5 mmol/l. The Kir6.2 subunit mRNA of the ATP-sensitive K ؉ channel was expressed in 42% of GE and GI neurons, but only 15% of nonglucosensing (NG) neurons. Glucokinase (GK), the putative glucosensing gatekeeper, was expressed in 64% of GE, 43% of GI, but only 8% of NG neurons and the GK inhibitor alloxan altered [Ca 2؉ ] i oscillations in ϳ75% of GK-expressing GE and GI neurons. Insulin receptor and GLUT4 mRNAs were coexpressed in 75% of GE, 60% of GI, and 40% of NG neurons, although there were no statistically significant intergroup differences. Hexokinase-I, GLUT3, and lactate dehydrogenase-A and -B were ubiquitous, whereas GLUT2, monocarboxylate transporters-1 and -2, and leptin receptor and GAD mRNAs were expressed less frequently and without apparent relationship to glucosensing capacity. Thus, although GK may mediate glucosensing in up to 60% of VMN neurons, other regulatory mechanisms are likely to control glucosensing in the remaining ones. Diabetes 53:549 -559, 2004

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Discrete brain areas express the insulin-responsive glucose transporter GLUT4

Cited by 123 publications

References 27 publications

Effects of insulin on long-term potentiation in hippocampal slices from diabetic rats

Effects of insulin on long-term potentiation in hippocampal slices from diabetic rats

The facilitative glucose transporter GLUT3: 20 years of distinction

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

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