Skip to main content
NCBI home page
British Journal of Pharmacology and Chemotherapy logoLink to British Journal of Pharmacology and Chemotherapy
. 1957 Sep;12(3):350–355. doi: 10.1111/j.1476-5381.1957.tb00147.x

The action of hypoglycaemic sulphonylureas on carbohydrate metabolism in the fasted rat

I Kelsey Fry, P H Wright
PMCID: PMC1509689  PMID: 13460243

Abstract

Tolbutamide and carbutamide given orally to fasted rats cause a rise in the liver glycogen content 1½ to 3½ hr. after administration of the drugs. Glycogen accumulates preferentially in the right lobe. Subcutaneously injected tolbutamide has the same effect. Both sulphonylureas cause inhibition of glucose-6-phosphatase activity of rat liver homogenates in vitro, but at drug concentrations comparable with those found in plasma of treated patients the degree of inhibition is less than 10%. Livers from treated rats show normal glucose-6-phosphatase activity. The glucose uptake of the isolated rat diaphragm is unaffected by the sulphonylureas added in vitro. Diaphragms from treated rats show normal glucose uptake in the presence or absence of insulin. The inferences to be drawn from these results are discussed in the light of previous work. It is concluded that the sulphonylureas exert hypoglycaemic action by inhibiting glycogenolysis and it is suggested that they might do so by inhibiting release of glucagon from the pancreas.

Full text

PDF
350

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ACKERMAN I. P., CONN J. W., FAJANS S. S., GITTLER R. D., HENNES A. R., JOHNSON R. D., LOUIS L. H., SELTZER H. S., WAJCHENBERG B. L. Metabolic effects of arylsulfonylurea compounds in normal men and in diabetic subjects. Metabolism. 1956 Nov;5(6 Pt 2):820–839. [PubMed] [Google Scholar]
  2. ANDERSON G. E., PERFETTO A. J., TERMINE C. M., MONACO R. R. Hypoglycemic action of orinase, effect on output of glucose by liver. Proc Soc Exp Biol Med. 1956 Jun;92(2):340–345. doi: 10.3181/00379727-92-22471. [DOI] [PubMed] [Google Scholar]
  3. ASHMORE J., CAHILL G. F., Jr, HASTINGS A. B. Inhibition of glucose-6-phosphatase by hypoglycemic sulfonylureas. Metabolism. 1956 Nov;5(6 Pt 2):774–777. [PubMed] [Google Scholar]
  4. ASHMORE J., CAHILL G. F., Jr, HASTINGS A. B., ZOTTU S. Studies on carbohydrate metabolism in rat liver slices. IX. Ionic and hormonal effects on phosphorylase and glycogen. J Biol Chem. 1957 Jan;224(1):237–250. [PubMed] [Google Scholar]
  5. BANDER A., SCHOLZ J. Spezielle pharmakologische Untersuchungen mit D 860. Dtsch Med Wochenschr. 1956 Jun 1;81(22):889–891. [PubMed] [Google Scholar]
  6. BERINGER A., LINDNER A. Zur Frage des Wirkungsmechanismus blutzuckersenkender Sulfonamide. Wien Klin Wochenschr. 1956 Apr 20;68(16):316–322. [PubMed] [Google Scholar]
  7. BERTHET J., MAKMAN M. H., SUTHERLAND E. W. Observations on the action of certain sulfonylurea derivatives. Metabolism. 1956 Nov;5(6 Pt 2):768–773. [PubMed] [Google Scholar]
  8. BERTRAM F., BENDFELDT E., OTTO H. Uber ein wirksames perorales Anti-diabeticum (BZ 55). Dtsch Med Wochenschr. 1955 Oct 7;80(40):1455–1460. doi: 10.1055/s-0028-1116223. [DOI] [PubMed] [Google Scholar]
  9. BUTTERFIELD W. J., CAMP J. L., HARDWICK C., HOLLING H. E. Clinical studies on the hypoglycaemic action of the sulphonylureas. Lancet. 1957 Apr 13;272(6972):753–756. doi: 10.1016/s0140-6736(57)91023-1. [DOI] [PubMed] [Google Scholar]
  10. CHULSKI T., FORIST A. A. pH-solubility relationships for 1-butyl-3-p-tolylsulfonylurea (orinase) and its metabolite, 1-butyl-3-p-carboxyphenylsulfonylurea. Metabolism. 1956 Nov;5(6 Pt 2):807–812. [PubMed] [Google Scholar]
  11. CLARKE D. W., DAVIDSON M., SCHONBAUM E., SENMAN H. Some in vitro studies with BZ-55. Can Med Assoc J. 1956 Jun 15;74(12):966–968. [PMC free article] [PubMed] [Google Scholar]
  12. DUNCAN G. G., LEVINE R. Symposium on clinical and experimental effects of sulfonylureas in diabetes mellitus; editorial statement. Metabolism. 1956 Nov;5(6 Pt 2):721–726. [PubMed] [Google Scholar]
  13. HAWKINS R. D., ASHWORTH M. A., HAIST R. E. The effect of BZ-55 (carbutamide) on glucose-6-phosphatase activity. Can Med Assoc J. 1956 Jun 15;74(12):972–973. [PMC free article] [PubMed] [Google Scholar]
  14. HOUSSAY B. A., PENHOS J. C. Action of the hypoglycemic sulfonyl compounds in hypophysectomized, adrenalectomized and depancreatized animals. Metabolism. 1956 Nov;5(6 Pt 2):727–732. [PubMed] [Google Scholar]
  15. KARK R. M., MOORHOUSE J. A. Physiologic actions of orinase and their relationship to the types of diabetes in man. Metabolism. 1956 Nov;5(6 Pt 2):847–863. [PubMed] [Google Scholar]
  16. LANG S., SHERRY S. Some effects of orinase in the rat. Metabolism. 1956 Nov;5(6 Pt 2):733–738. [PubMed] [Google Scholar]
  17. MILLER W. L., Jr, DULIN W. E. Orinase, a new oral hypoglycemic compound. Science. 1956 Apr 6;123(3197):584–585. doi: 10.1126/science.123.3197.584. [DOI] [PubMed] [Google Scholar]
  18. MOHNIKE G., KNITSCH W. Uber die Wirkung von D 860 an Leberschnitten. Dtsch Med Wochenschr. 1956 Jun 1;81(22):891–891. [PubMed] [Google Scholar]
  19. STRICKLAND K. P., THOMPSON R. H., WEBSTER G. R. The action of the phosphatases of human brain on lipid phosphate esters. J Neurol Neurosurg Psychiatry. 1956 Feb;19(1):12–16. doi: 10.1136/jnnp.19.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SWANSON M. A. Phosphatases of liver. I. Glucose-6-phosphatase. J Biol Chem. 1950 Jun;184(2):647–659. [PubMed] [Google Scholar]
  21. TYBERGHEIN J. M., HALSEY Y. D., WILLIAMS R. H. Action of butyltolylsulfonylurea on liver glycogenolysis. Proc Soc Exp Biol Med. 1956 Jun;92(2):322–324. doi: 10.3181/00379727-92-22465. [DOI] [PubMed] [Google Scholar]
  22. VALLANCE-OWEN J., HURLOCK B. Estimation of plasma-insulin by the rat diaphragm method. Lancet. 1954 Jan 9;266(6802):68–70. doi: 10.1016/s0140-6736(54)90820-x. [DOI] [PubMed] [Google Scholar]
  23. VAUGHAN M. In vitro studies on the action of sulfonamide hypoglycemic agents. Science. 1956 May 18;123(3203):885–886. doi: 10.1126/science.123.3203.885. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology and Chemotherapy are provided here courtesy of The British Pharmacological Society

RESOURCES