RT Journal Article
SR Electronic
T1 CARBOHYDRATE METABOLISM IN NORMAL AND HYPERGLYCEMIC ANIMALS TREATED WITH 1-METHYL-4-(3-METHYL-5-ISOXAZOLYL) PYRIDINIUM CHLORIDE AND PHENFORMIN
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 536
OP 545
VO 177
IS 3
A1 D. A. BLICKENS
A1 S. J. RIGGI
YR 1971
UL http://jpet.aspetjournals.org/content/177/3/536.abstract
AB 1-Methyl-4-(3-methyl-5-isoxazolyl)-pyridinium chloride (I) has been reported to be an orally active hypoglycemic agent in guinea pigs, mice, cockerels and alloxan-treated rats and mice. Hypoglycemia in normal mice was associated with metabolic alterations similar to those occurring after phenformin treatment. The present studies were conducted to evaluate the metabolic effects of I in several experimental hyperglycemic models in an attempt to further elucidate the mechanism of action of I. Blood glucose was decreased after I administration to partially eviscerated guinea pigs, obese diabetic mice (C57BL/Ks-db) and alloxan- or streptozotocintreated rats suggesting that hypoglycemia is independent of pancreatic insulin release. Increased blood lactate in normal and alloxan-treated rats after I or phenformin treatment suggested an enhanced anaerobic glycolysis. Decreased glycosuria in alloxan-treated rats after I or phenformin and in streptozotocin-treated rats after I treatment essentially eliminated urinary glucose as contributory to hypoglycemia. After a single dose of I or phenformin in hyperglycemic rats, liver glycogen decreased and skeletal muscle glycogen increased. These data suggest that liver glycogenolysis was unimpaired and that increased skeletal muscle uptake may play a major role in development of hypoglycemia. These and previous studies indicated that I and phenformin exert similar effects on carbohydrate metabolism in normal and hyperglycemic states. © 1971 by The Williams & Wilkins Co.