Stimulation by hexose esters of lactate production by rat erythrocytes: insensitivity to 3-O-methyl-D-glucose and inhibition by 2-deoxy-D-glucose and its tetraacetic ester.
Selected esters of D-glucose were recently proposed as tools to provide the sugar to cells, whilst bypassing the carrier system for hexose transport across the plasma membrane. In the present study, alpha-D-glucose pentaacetate, beta-D-glucose pentaacetate, alpha-D-mannose pentaacetate and, to a lesser extent, 6-O-acetyl-D-glucose, all tested at a 1.7 mM concentration, were found to increase lactate production above basal value in rat erythrocytes. Over 90 min incubation, the increment in lactate production ranged from about 1.2 (alpha-D-glucose pentaacetate) to 0.6 (6-O-acetyl-D-glucose) micromol/microl of erythrocytes. Little or no change in lactate production was observed in cells exposed to beta-L-glucose pentaacetate, alpha-D-glucose pentaethylsuccinate, alpha-D-galactose pentaacetate or beta-D-galactose pentaacetate. The metabolic response to alpha-D-glucose pentaacetate was resistant to 3-O-methyl-D-glucose (10-80 mM) which suppressed, however, that evoked by D-glucose. D-mannoheptulose (10 mM) virtually failed to affect the response to D-glucose and its pentaacetate ester. On the contrary, 2-deoxy-D-glucose (10.6 mM) inhibited to the same relative extent (55% decrease) lactate production in erythrocytes exposed to either unesterified D-glucose or alpha-D-glucose pentaacetate. The tetraacetic ester of 2-deoxy-D-glucose was more efficient than unesterified 2-deoxy-D-glucose in inhibiting lactate production from alpha-D-glucose pentaacetate. It is proposed that selected esters of saccharides represent useful tools to bypass defects in hexose transport, and to increase their nutritional or therapeutic efficiency.
Ladrière
L
L
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Kadiata
M M
MM
Kirk
O
O
Malaisse
W J
WJ
D019325:3-O-Methylglucose / Q000494:pharmacology*; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D004952:Esters; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives / Q000494:pharmacology; D006601:Hexoses / Q000494:pharmacology*; D019344:Lactic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008356:Mannoheptulose / Q000494:pharmacology; D008358:Mannose / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar
D004952:Esters; D006601:Hexoses; D019325:3-O-Methylglucose; C105128:glucose pentaacetate; D019344:Lactic Acid; D008356:Mannoheptulose; C026877:galactose peracetate; D003847:Deoxyglucose; D005947:Glucose; D008358:Mannose; D005690:Galactose