Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain—an immunohistochemical study

Arluison, Michel; Quignon, Monique; Nguyên, Philippe; Thorens, Bernard; Leloup, Corinne; Pénicaud, Luc

doi:10.1016/j.jchemneu.2004.05.009

Cited by 134 publications

(100 citation statements)

References 70 publications

(75 reference statements)

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“…This can be not only due to the role of Glut2 in hepatoportal glucodetection but also due to a role in central glucodetection, as this transporter is also expressed in the hypothalamus and the brainstem. 63 A role in central glucose sensing was indeed evidenced by the failure of intracerebroventricular 2-DG injections to stimulate glucagon secretion in these mutant mice. 64 Furthermore, the analysis of c-fospositive cells in response to intraperitoneal 2-DG injections indicated a decreased number of activated cells in the brainstem, in particular in the NTS and the dorsal motor nucleus of the vagus in the Glut2-null mice.…”

Section: S64mentioning

confidence: 93%

“…Attempts at localizing Glut2 in the brain has failed to show its expression in POMC or NPY neurons, although it was found to be associated with other hypothalamic and brainstem structures 63,[82][83][84][85] and expressed by neurons, astrocytes, endothelial cells and tanycytes of the third ventricle. [86][87][88] Thus, the regulation of orexigenic and anorexigenic peptide expressions by Glut2-dependent sensors may be controlled indirectly, possibly even by sensors located in other brain regions, such as the brainstem, in possible agreement with the reported presence in this structure of glucose-sensitive neurons that control feeding.…”

Section: Feeding Controlmentioning

confidence: 99%

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Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Thorens

2008

Int J Obes

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The control of body weight and of blood glucose concentrations depends on the exquisite coordination of the function of several organs and tissues, in particular the liver, muscle and fat. These organs and tissues have major roles in the use and storage of nutrients in the form of glycogen or triglycerides and in the release of glucose or free fatty acids into the blood, in periods of metabolic needs. These mechanisms are tightly regulated by hormonal and nervous signals, which are generated by specialized cells that detect variations in blood glucose or lipid concentrations. The hormones insulin and glucagon not only regulate glycemic levels through their action on these organs and the sympathetic and parasympathetic branches of the autonomic nervous system, which are activated by glucose or lipid sensors, but also modulate pancreatic hormone secretion and liver, muscle and fat glucose and lipid metabolism. Other signaling molecules, such as the adipocyte hormones leptin and adiponectin, have circulating plasma concentrations that reflect the level of fat stored in adipocytes. These signals are integrated at the level of the hypothalamus by the melanocortin pathway, which produces orexigenic and anorexigenic neuropeptides to control feeding behavior, energy expenditure and glucose homeostasis. Work from several laboratories, including ours, has explored the physiological role of glucose as a signal that regulates these homeostatic processes and has tested the hypothesis that the mechanism of glucose sensing that controls insulin secretion by the pancreatic beta-cells is also used by other cell types. I discuss here evidence for these mechanisms, how they integrate signals from other nutrients such as lipids and how their deregulation may initiate metabolic diseases.

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Section: S64mentioning

confidence: 93%

Section: Feeding Controlmentioning

confidence: 99%

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Thorens

2008

Int J Obes

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“…In rats, a careful immunohistochemical mapping of GLUT2 expression at the light and electron microscopy levels revealed its presence in most brain structures, and expression was found in neurons, astrocytes, endothelial cells and tanycytes, which are specialised astrocytes lining the lower part of the third ventricle [60][61][62]. In mice, using a genetic reporter system in which a fluorescent protein is expressed under the control of the Glut2 promoter (Glut2-Cre transgenic mice crossed with Rosa26tdTomato mice), the distribution of GLUT2 expressing cells in the brain was found to be very similar to that of the rat [63].…”

Section: Glut2 In the Nervous Systemmentioning

confidence: 99%

GLUT2, glucose sensing and glucose homeostasis

2014

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The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

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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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Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain—an immunohistochemical study

Cited by 134 publications

References 70 publications

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

GLUT2, glucose sensing and glucose homeostasis

The facilitative glucose transporter GLUT3: 20 years of distinction

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