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.