scholarly journals Role of Central Nervous System Glucagon-Like Peptide-1 Receptors in Enteric Glucose Sensing

Diabetes ◽  
2008 ◽  
Vol 57 (10) ◽  
pp. 2603-2612 ◽  
Author(s):  
C. Knauf ◽  
P. D. Cani ◽  
D.-H. Kim ◽  
M. A. Iglesias ◽  
C. Chabo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glucose Sensing ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Central Nervous System Regulation of Intestinal Lipoprotein Metabolism by Glucagon-Like Peptide-1 via a Brain–Gut Axis

2015 ◽  
Vol 35 (5) ◽  
pp. 1092-1100 ◽  
Author(s):  
Sarah Farr ◽  
Christopher Baker ◽  
Mark Naples ◽  
Jennifer Taher ◽  
Jahangir Iqbal ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lipoprotein Metabolism ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Effects of glucose and insulin on glucokinase activity in rat hypothalamus

2007 ◽  
Vol 193 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Carmen Sanz ◽  
Isabel Roncero ◽  
Patricia Vázquez ◽  
M Angeles Navas ◽  
Enrique Blázquez
Keyword(s):  
Enzyme Activities ◽  
Physiological Model ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
Biological Models ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain ◽  
Hypothalamic Slices

In an attempt to study the role of glucokinase (GK) and the effects of glucose and peptides on GK gene expression and on the activity of this enzyme in the hypothalamus, we used two kinds of biological models: hypothalamic GT1-7 cells and rat hypothalamic slices. The expression of the GK gene in GT1-7 cells was reduced by insulin (INS) and was not modified by different glucose concentrations, while GK enzyme activities were significantly reduced by the different peptides. Interestingly, a distinctive pattern of GK activities between the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) were found, with higher enzyme activities in the VMH as the glucose concentrations rose, while LH enzyme activities decreased at 2.8 and 20 mM glucose, the latter effect being prevented by incubation with INS. These effects were produced only by d-glucose and the modifications found were due to GK, but not to other hexokinases. In addition, GK activities in the VMH and the LH were reduced by glucagon-like peptide 1, leptin, orexin B, INS, and neuropeptide Y (NPY), but this effect was only statistically significant for NPY in LH. Our results indicate that the effects of both glucose and peptides occur on GK enzyme activities rather than on GK gene transcription. Moreover, the effects of glucose and INS on GK activity suggest that in the brain GK behaves in a manner opposite to that in the liver, which might facilitate its role in glucose sensing. Finally, hypothalamic slices seem to offer a good physiological model to discriminate the effects between different areas.

scholarly journals Direct Control of Brown Adipose Tissue Thermogenesis by Central Nervous System Glucagon-Like Peptide-1 Receptor Signaling

Diabetes ◽  
2012 ◽  
Vol 61 (11) ◽  
pp. 2753-2762 ◽  
Author(s):  
S. H. Lockie ◽  
K. M. Heppner ◽  
N. Chaudhary ◽  
J. R. Chabenne ◽  
D. A. Morgan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Receptor Signaling ◽  
Direct Control ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Peripheral and Central GLP-1 Receptor Populations Mediate the Anorectic Effects of Peripherally Administered GLP-1 Receptor Agonists, Liraglutide and Exendin-4

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3103-3112 ◽  
Author(s):  
Scott E. Kanoski ◽  
Samantha M. Fortin ◽  
Myrtha Arnold ◽  
Harvey J. Grill ◽  
Matthew R. Hayes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
Vagal Afferents ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Higher Doses ◽  
Cns Delivery

The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists, exendin-4 and liraglutide, suppress food intake and body weight. The mediating site(s) of action for the anorectic effects produced by peripheral administration of these GLP-1R agonists are not known. Experiments addressed whether food intake suppression after ip delivery of exendin-4 and liraglutide is mediated exclusively by peripheral GLP-1R or also involves direct central nervous system (CNS) GLP-1R activation. Results showed that CNS delivery [third intracerebroventricular (3rd ICV)] of the GLP-1R antagonist exendin-(9–39) (100 μg), attenuated the intake suppression by ip liraglutide (10 μg) and exendin-4 (3 μg), particularly at 6 h and 24 h. Control experiments show that these findings appear to be based neither on the GLP-1R antagonist acting as a nonspecific competing orexigenic signal nor on blockade of peripheral GLP-1R via efflux of exendin-(9–39) to the periphery. To assess the contribution of GLP-1R expressed on subdiaphragmatic vagal afferents to the anorectic effects of liraglutide and exendin-4, food intake was compared in rats with complete subdiaphragmatic vagal deafferentation and surgical controls after ip delivery of the agonists. Both liraglutide and exendin-4 suppressed food intake at 3 h, 6 h, and 24 h for controls; for subdiaphragmatic vagal deafferentation rats higher doses of the GLP-1R agonists were needed for significant food intake suppression, which was observed at 6 h and 24 h after liraglutide and at 24 h after exendin-4. Conclusion: Food intake suppression after peripheral administration of exendin-4 and liraglutide is mediated by activation of GLP-1R expressed on vagal afferents as well as direct CNS GLP-1R activation.

scholarly journals MON-666 Glucokinase Within the Hypothalamic Paraventricular Nucleus Is Important in GLP-1 Release

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Risheka Ratnasabapathy
Keyword(s):  
Glucose Tolerance ◽  
Paraventricular Nucleus ◽  
Glucose Sensing ◽  
Hypothalamic Paraventricular Nucleus ◽  
Oral Glucose ◽  
Insulin Synthesis ◽  
Glucose Intake ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract When glucose is taken orally more insulin is secreted than when glucose is injected directly into the bloodstream. This is known as the incretin effect. Glucagon like peptide 1 (GLP-1) is one of the hormones responsible for this effect. GLP-1 is released from enteroendocrine L-cells in the gut in response to oral glucose intake. GLP-1 increases insulin synthesis and secretion. Release of GLP-1 is thought to be solely dependent upon gastrointestinal tract mechanisms. Here we identify a brain mechanism via the hypothalamic paraventricular nucleus (PVN) which is important in the release of GLP-1 in response to oral glucose. The role of the paraventricular nucleus in glucose homeostasis was previously unknown. We found that a glucokinase dependent glucose sensing mechanism in the PVN works in conjunction with the gut to regulate GLP-1 release. We show that increasing expression of GK (sense GK, sGK) into the PVN improves glucose tolerance (15 minutes glucose: GFP: 8.93±0.27mmol/L, n=11; sGK: 7.72±0.22mmol/L, n=12; p<0.01 and 15 minutes insulin GFP: 2.84±0.14mmol/L, n=11; sGK: 3.73±0.27mmol/L, n=12; p<0.01) and increases GLP-1 release in response to oral glucose (GFP: 6.16±0.18mmol/L, n=11; sGK: 6.90±0.26mmol/L, n=12; p<0.01). On the contrary decreasing expression of GK (antisense GK, asGK) in the PVN worsens glucose tolerance (30 minutes glucose: GFP: 8.22±0.28mmol/L; asGK: 9.46±0.24mmol/L, n=8; p<0.01 and 15 minutes insulin: GFP: 4.07±0.37mmol/L; asGK: 2.25±0.17mmol/L, n=8; p<0.001) and blunts (GLP-1 release 30 minutes GLP-1: GFP: 6.93±0.25pMol/L, n=8; p<0.01 asGK: 5.47±0.13pMol/L, n=8; p<0.001). Our results demonstrate that glucosensitive GK neurones in the PVN, are important to the response to oral glucose and the subsequent release of GLP-1.

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