RT Journal Article
SR Electronic
T1 Effect of a new hypoglycemic agent (MDL-310) on glucose metabolism.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 571
OP 576
VO 235
IS 3
A1 K M Robinson
A1 A J Payne
A1 S L Zehr
A1 B L Rhinehart
YR 1985
UL http://jpet.aspetjournals.org/content/235/3/571.abstract
AB 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.