Acceleration of glycolysis in erythrocytes by the antidiabetic agent M16209.
The effects of M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin), an antidiabetic agent and aldose reductase inhibitor, on glycolysis were studied in rat and human erythrocytes in vitro. M16209 increased lactate production from glucose when incubated with rat and human erythrocytes, and also increased glucose consumption in rat erythrocytes. The rates of production of lactate in rat erythrocytes treated with M16209 at 10, 25 and 50 microM were 113, 118 and 123%, respectively, of those in vehicle treated cells. Sorbinil (aldose reductase inhibitor), tolbutamide (sulfonylurea), and buformine (biguanide) did not increase lactate production in rat erythrocytes when tested at 50 microM. On the other hand, M16209 did not affect lactate production from D-glyceraldehyde in rat erythrocytes. At 100 microM the agent decreased both glucose-6-phosphate and fructose-6-phosphate in rat erythrocytes, and increased fructose-1,6-bisphosphate; at 10 microM it also increased 6-phosphofructokinase activity in rat hemolysates. These findings suggest that M16209 accelerates glycolysis in erythrocytes via activation of 6-phosphofructokinase.
Hashimoto
K
K
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
Murakami
N
N
Ohta
M
M
Kato
K
K
Mizota
M
M
Miwa
I
I
Okuda
J
J
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005985:Glyceraldehyde / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D001572:Benzofurans; D006827:Hydantoins; D007004:Hypoglycemic Agents; D007093:Imidazoles; D048289:Imidazolidines; C068409:M 16209; D019344:Lactic Acid; D005985:Glyceraldehyde; D014044:Tolbutamide; D000449:Aldehyde Reductase; D010732:Phosphofructokinase-1; C026411:sorbinil; D005947:Glucose