Document Detail


Sodium-coupled glucose cotransporters contribute to hypothalamic glucose sensing.
MedLine Citation:
PMID:  17130483     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Specialized neurons within the hypothalamus have the ability to sense and respond to changes in ambient glucose concentrations. We investigated the mechanisms underlying glucose-triggered activity in glucose-excited neurons, using primary cultures of rat hypothalamic neurons monitored by fluorescence calcium imaging. We found that 35% (738 of 2,139) of the neurons were excited by increasing glucose from 3 to 15 mmol/l, but only 9% (6 of 64) of these glucose-excited neurons were activated by tolbutamide, suggesting the involvement of a ATP-sensitive K(+) channel-independent mechanism. alpha-Methylglucopyranoside (alphaMDG; 12 mmol/l), a nonmetabolizable substrate of sodium glucose cotransporters (SGLTs), mimicked the effect of high glucose in 67% of glucose-excited neurons, and both glucose- and alphaMDG-triggered excitation were blocked by Na(+) removal or by the SGLT inhibitor phloridzin (100 nmol/l). In the presence of 0.5 mmol/l glucose and tolbutamide, responses could also be triggered by 3.5 mmol/l alphaMDG, supporting a role for an SGLT-associated mechanism at low as well as high substrate concentrations. Using RT-PCR, we detected SGLT1, SGLT3a, and SGLT3b in both cultured neurons and adult rat hypothalamus. Our findings suggest a novel role for SGLTs in glucose sensing by hypothalamic glucose-excited neurons.
Authors:
Dervla O'Malley; Frank Reimann; Anna K Simpson; Fiona M Gribble
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes     Volume:  55     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-01-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3381-6     Citation Subset:  AIM; IM    
Affiliation:
Cambridge Institute of Medical Research, Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, U.K.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / physiology
Cells, Cultured
Glucose / pharmacology*
Hypothalamus / drug effects,  physiology*
Kinetics
Methylglucosides / pharmacology
Neurons / drug effects,  physiology*
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Sodium-Glucose Transport Proteins / genetics*
Tolbutamide / pharmacology
Grant Support
ID/Acronym/Agency:
071187//Wellcome Trust
Chemical
Reg. No./Substance:
0/Methylglucosides; 0/Sodium-Glucose Transport Proteins; 50-99-7/Glucose; 64-77-7/Tolbutamide; 7440-70-2/Calcium
Comments/Corrections

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