Sodium-coupled glucose transporter as a functional glucose sensor of retinal microvascular circulation.
To clarify the function of the Na(+)-coupled glucose transporter in the regulation of cellular tone of cultured retinal pericytes, we investigated the effects of extracellular glucose concentration on cell size. The surface area and diameter of cultured bovine retinal pericytes under different glucose concentrations were measured by using a light microscope with a digital camera. We also examined the effects of extracellular Na(+) and Ca(2+), inhibitors of the Na(+)-coupled glucose transporter and Na(+)-Ca(2+) exchanger, a Ca(2+) channel blocker, and nonmetabolizable sugars on cell size. The surface area and diameter of the cells changed according to extracellular glucose concentrations. alpha-Methyl glucoside, which enters the cell through the Na(+)-coupled glucose transporter, induced cellular contraction. However, the cells did not contract in response to 2-deoxyglucose, which enters the cell through a facilitated glucose transporter. Glucose-induced cellular contraction was abolished in the absence of extracellular Na(+) and Ca(2+). Moreover, phlorizin, an inhibitor of the Na(+)-coupled glucose transporter, and 2',4'-dichlorobenzamil-HCl, an inhibitor of the Na(+)-Ca(2+) exchanger, also abolished glucose-induced cellular contraction, whereas nicardipine, a Ca(2+) channel blocker, did not. Our results indicate that high extracellular glucose concentrations induce contraction of bovine retinal pericytes via Na(+) entry through a Na(+)-coupled glucose transporter, suggesting that the Na(+)-coupled glucose transporter may act as a functional glucose sensor of retinal microvascular circulation.>
Wakisaka
M
M
Department of Medicine and Clinical Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. wakisaka@intmed2.med.kyushu-u.ac.jp
Kitazono
T
T
Kato
M
M
Nakamura
U
U
Yoshioka
M
M
Uchizono
Y
Y
Yoshinari
M
M
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D048429:Cell Size / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D008757:Methylglucosides / Q000494:pharmacology; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C027020:methylglucoside; D000584:Amiloride; C064515:2',4'-dichlorobenzamil amiloride; D003847:Deoxyglucose; D012964:Sodium; D010695:Phlorhizin; D005947:Glucose; D002118:Calcium