Document Detail


The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine.
MedLine Citation:
PMID:  22495587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intestinal enteroendocrine cells (IECs) secrete gut peptides in response to both nutrients and non-nutrients. Glucose and amino acids both stimulate gut peptide secretion. Our hypothesis was that the facilitative glucose transporter, GLUT2, could act as a glucose sensor and the calcium-sensing receptor, CasR, could detect amino acids in the intestine to modify gut peptide secretion. We used isolated loops of rat small intestine to study the secretion of gluco-insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) secretion stimulated by luminal perfusion of nutrients or bile acid. Inhibition of the sodium-dependent glucose cotransporter 1 (SGLT1) with phloridzin partially inhibited GIP, GLP-1 and PYY secretion by 45%, suggesting another glucose sensor might be involved in modulating peptide secretion. The response was completely abolished in the presence of the GLUT2 inhibitors phloretin or cytochalasin B. Given that GLUT2 modified gut peptide secretion stimulated by glucose, we investigated whether it was involved in the secretion of gut peptide by other gut peptide secretagogues. Phloretin completely abolished gut peptide secretion stimulated by artificial sweetener (sucralose), dipeptide (glycylsarcosine), lipid (oleoylethanolamine), short chain fatty acid (propionate) and major rat bile acid (taurocholate) indicating a fundamental position for GLUT2 in the gut peptide secretory mechanism. We investigated how GLUT2 was able to influence gut peptide secretion mediated by a diverse range of stimulators and discovered that GLUT2 affected membrane depolarisation through the closure of K+(ATP)-sensitive channels. In the absence of SGLT1 activity (or presence of phloridzin), the secretion of GIP, GLP-1 and PYY was sensitive to K+(ATP)-sensitive channel modulators tolbutamide and diazoxide. L-amino acids phenylalanine (Phe), tryptophan (Trp), asparagine (Asn), arginine (Arg) and glutamine (Gln) also stimulated GIP, GLP-1 and PYY secretion, which was completely abolished when extracellular Ca2+ was absent. The gut peptide response stimulated by the amino acids was also blocked by the CasR inhibitor Calhex 231 and augmented by the CasR agonist NPS-R568. GLUT2 and CasR regulate K- and L-cell activity in response to nutrient and non-nutrient stimuli.
Authors:
Oliver J Mace; Marcus Schindler; Sonal Patel
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2012-04-10
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-18     Completed Date:  2013-06-17     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2917-36     Citation Subset:  IM    
Affiliation:
Prosidion, Windrush Court, Oxford OX4 6LT, UK. olivermace@googlemail.com
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism
Aniline Compounds / pharmacology
Animals
Benzamides / pharmacology
Calcium / metabolism
Cyclohexylamines / pharmacology
Cytochalasin B / pharmacology
Enteroendocrine Cells / metabolism*
Glucose Transporter Type 2 / agonists,  antagonists & inhibitors,  metabolism*
Incretins / metabolism,  secretion*
Intestine, Small / metabolism,  secretion*
KATP Channels / metabolism
Male
Phloretin / pharmacology
Phlorhizin / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Calcium-Sensing / agonists,  antagonists & inhibitors,  metabolism*
Sodium-Glucose Transporter 1 / antagonists & inhibitors,  metabolism
Sucrose / analogs & derivatives,  pharmacology
Sweetening Agents / pharmacology
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Aniline Compounds; 0/Benzamides; 0/Cyclohexylamines; 0/Glucose Transporter Type 2; 0/Incretins; 0/KATP Channels; 0/N(1)-(4-chlorobenzoyl)-N(2)-(1-(1-naphthyl)ethyl)-1,2-diaminocyclohexane; 0/N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; 0/Receptors, Calcium-Sensing; 0/Sodium-Glucose Transporter 1; 0/Sweetening Agents; 14930-96-2/Cytochalasin B; 56038-13-2/trichlorosucrose; 57-50-1/Sucrose; 60-81-1/Phlorhizin; 60-82-2/Phloretin; 7440-70-2/Calcium
Comments/Corrections
Comment In:
J Physiol. 2012 Jun 15;590(Pt 12):2825-6   [PMID:  22707587 ]

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