Glipizide and hepatic glycogenolysis.

Glipizide, a new sulfonylurea recently introduced for the treatment of diabetes, was studied to check its possible extrapancreatic effects. Rats were given a subcutaneous injection of 1 g/kg glucosamine: this dose caused marked hyperglycemia and a decrease in hepatic glycogen, but does not alter blood insulin levels. Pretreatment with i.v. dose of 37.5 microgram/kg glipizide 1 hour before the glucosamine load, significantly inhibits the hyperglycemia and the decrease of hepatic glycogen. This dose of glipizide does not affect blood sugar levels, although it does induce a transient rise in insulin secretion, which lasts no more than 10 minutes after administration. Since glucosamine was administered 1 hour after the sulfonylurea by which time the interference of insulin was no longer felt, it may be concluded that in the experiment described, glipizide seems to have some other action apart from stimulating insulin secretion.

Effect of glipizide on muscle metabolism in vitro.

This paper contains the results of further investigation on the possible extrapancreatic activity of glipizide. An in vitro method, using isolated rat diaphragm was selected. Muscle uptake of C14 glucose and output of labelled CO2, were measured. Insulin was used as the reference substance. The results of our experiments indicate that there is a qualitative difference in the effects of the two experimental situations. However, from these findings it may be assumed that glipizide facilitates the uptake and metabolism of glucose in muscle, thus demonstrating an extrapancreatic effect, which contributes to the hypoglycemic activity of the drug.