Intracerebroventricular Administration of Antisense Oligodeoxynucleotide against GLUT2 Glucose Transporter mRNA Reduces Food Intake, Body Weight Change and Glucoprivic Feeding Response in Rats ,

Wan, Hong; Hulsey, Martin G.; Martin, Roy J.

doi:10.1093/jn/128.2.287

Cited by 46 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[65] injections of specific antisense oligonucleotides to silence Glut2 expression. In the first study this led to reduced body weight with no change in feeding and a reduced insulin response to intracarotid glucose administration.…”

Section: Glucose Sensing Feeding and Thermogenesismentioning

confidence: 99%

GLUT2, glucose sensing and glucose homeostasis

2014

View full text Add to dashboard Cite

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.

show abstract

Section: Glucose Sensing Feeding and Thermogenesismentioning

confidence: 99%

GLUT2, glucose sensing and glucose homeostasis

2014

View full text Add to dashboard Cite

show abstract

“…For example, 2-deoxyglucose, a metabolite that blocks glucose metabolism by inhibiting early steps in glycolysis, potently stimulates food intake when given directly into the CNS [52] or peripherally [53]. Further, genetic models lacking glucose transporter 2 (GLUT2) are also hyperphagic and obese [52,[54][55][56].…”

Section: Hormones and Nutrientsmentioning

confidence: 99%

Hypothalamic control of energy and glucose metabolism

Sisley

Sandoval

2011

Rev Endocr Metab Disord

View full text Add to dashboard Cite

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

show abstract

“…This led to a reduction in feeding and body weight and a suppression of the feeding response to 2-DG. 80 In the Glut2-null (ripglut1;glut2 À/À ) mice ad libitum feeding was B20% higher than in controls, and, after a 24 h fast, they initiated feeding less rapidly than control mice but progressively ate more so that cumulative food intake over 48 h was again higher than that of control mice. 81 The feeding responses to intracerebroventricular glucose or 2-DG was also lost in these mutant mice.…”

Section: Feeding Controlmentioning

confidence: 99%

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Thorens

2008

Int J Obes

View full text Add to dashboard Cite

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.

show abstract

Intracerebroventricular Administration of Antisense Oligodeoxynucleotide against GLUT2 Glucose Transporter mRNA Reduces Food Intake, Body Weight Change and Glucoprivic Feeding Response in Rats ,

Cited by 46 publications

References 34 publications

GLUT2, glucose sensing and glucose homeostasis

GLUT2, glucose sensing and glucose homeostasis

Hypothalamic control of energy and glucose metabolism

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Contact Info

Product

Resources

About