Effect of a new hypoglycemic agent (MDL-310) on glucose metabolism.
N-[3-(dimethylamino)-2-propoxy-2-propenylidene]- N-methylmethanaminium as the iodide or camsylate salt (MDL-310) is a newly reported chemical which has been shown to produce hypoglycemia in vivo. The studies reported here describe in vivo and in vitro effects of MDL-310 on carbohydrate metabolism. In nonfasted mice, MDL-310 decreased liver glycogen and then produced hypoglycemia, concomitant with a near total depletion of liver glycogen stores. In fasted rats, nonhypoglycemic doses of MDL-310 increased glucose production and utilization as determined by tracer studies with [6-3H]glucose. Hypoglycemic doses decreased glucose production and increased blood lactate, which suggests an inhibition of gluconeogenesis. In isolated rat hepatocytes MDL-310, at concentrations of greater than or equal to 5 X 10(-6) M, inhibited gluconeogenesis from lactate (10 mM) plus pyruvate (2 mM). We conclude that the primary action of MDL-310 is to increase glucose utilization and that decreased production due to the inhibition of gluconeogenesis is involved in the hypoglycemic action. A single metabolic action of MDL-310 to increase glycolytic metabolism of glucose is proposed which could explain both the increase in glucose utilization and decrease in glucose production.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007004:Hypoglycemic Agents; D007773:Lactates; D000644:Quaternary Ammonium Compounds; D019344:Lactic Acid; D006003:Glycogen; C047599:MDL 310; D005947:Glucose