HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by O’Malley, D. Articles by Gribble, F. M. Search for Related Content PubMed PubMed Citation Articles by O’Malley, D. Articles by Gribble, F. M. Social Bookmarking                What's this?

Sodium-Coupled Glucose Cotransporters Contribute to Hypothalamic Glucose Sensing

From the Department of Clinical Biochemistry, Cambridge Institute of Medical Research, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K

Address correspondence and reprint requests to Dr. Fiona Gribble, Cambridge Institute of Medical Research, Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2XY, U.K. E-mail: fmg23{at}cam.ac.uk

Abbreviations: [Ca²⁺]_i, intracellular Ca²⁺ concentration; K_ATP channel, ATP-sensitive K⁺ channel; DMEM, Dulbecco’s modified Eagle’s medium; MDG, -methylglucopyranoside; 3-O-MDG, 3-O-methyl-D-glucopyranose; SGLT, sodium-coupled glucose cotransporter

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. -Methylglucopyranoside (MDG; 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 MDG-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 MDG, 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?