Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1976 Aug;57(4):573–579. doi: 10.1111/j.1476-5381.1976.tb10387.x

Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions.

Z Merali, R L Singhal
PMCID: PMC1667028  PMID: 183849

Abstract

Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc.

Full text

PDF

Selected References

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

  1. Birnbaumer L., Pohl S. L., Rodbell M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. II. Comparison between glucagon- and fluoride-stimulated activities. J Biol Chem. 1971 Mar 25;246(6):1857–1860. [PubMed] [Google Scholar]
  2. Bitensky M. W., Gorman R. E., Neufeld A. H. Selective effects of insulin on hepatic epinephrine responsive adenyl cyclase activity. Endocrinology. 1972 May;90(5):1331–1335. doi: 10.1210/endo-90-5-1331. [DOI] [PubMed] [Google Scholar]
  3. Bremner I. Heavy metal toxicities. Q Rev Biophys. 1974 Feb;7(1):75–124. doi: 10.1017/s0033583500001359. [DOI] [PubMed] [Google Scholar]
  4. COTZIAS G. C., BORG D. C., SELLECK B. Virtual absence of turnover in cadmium metabolism: Cd109 studies in the mouse. Am J Physiol. 1961 Nov;201:927–930. doi: 10.1152/ajplegacy.1961.201.5.927. [DOI] [PubMed] [Google Scholar]
  5. Colucci A. V., Winge D., Krasno J. Cadmium accumulation in rat liver. Arch Environ Health. 1975 Mar;30(3):153–157. doi: 10.1080/00039896.1975.10666665. [DOI] [PubMed] [Google Scholar]
  6. Exton J. H. Gluconeogenesis. Metabolism. 1972 Oct;21(10):945–990. doi: 10.1016/0026-0495(72)90028-5. [DOI] [PubMed] [Google Scholar]
  7. Exton J. H., Park C. R. Control of gluconeogenesis in liver. II. Effects of glucagon, catecholamines, and adenosine 3',5'-monophosphate on gluconeogenesis in the perfused rat liver. J Biol Chem. 1968 Aug 25;243(16):4189–4196. [PubMed] [Google Scholar]
  8. Ghafghazi T., Mennear J. H. Effects of acute and subacute cadmium administration on carbohydrate metabolism in mice. Toxicol Appl Pharmacol. 1973 Oct;26(2):231–240. doi: 10.1016/0041-008x(73)90256-1. [DOI] [PubMed] [Google Scholar]
  9. Ghagghazi T., Mennear J. H. The inhibitory effect of cadmium on the secretory activity of the isolated perfused rat pancreas. Toxicol Appl Pharmacol. 1975 Jan;31(1):134–142. doi: 10.1016/0041-008x(75)90061-7. [DOI] [PubMed] [Google Scholar]
  10. Greengard O. The hormonal regulation of enzymes in penatal and postnatal rat liver. Effects of adenosine 3',5'-(cyclic)-monophosphate. Biochem J. 1969 Oct;115(1):19–24. doi: 10.1042/bj1150019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HILL C. H., MATRONE G., PAYNE W. L., BARBER C. W. In vivo interactions of cadmium with copper, zinc and iron. J Nutr. 1963 Jul;80:227–235. doi: 10.1093/jn/80.3.227. [DOI] [PubMed] [Google Scholar]
  12. Halsted J. A., Smith J. C., Jr, Irwin M. I. A conspectus of research on zinc requirements of man. J Nutr. 1974 Mar;104(3):345–378. doi: 10.1093/jn/104.3.345. [DOI] [PubMed] [Google Scholar]
  13. Havu N. Sulfhydryl inhibitors and pancreatic islet tissue. Acta Endocrinol Suppl (Copenh) 1969;139:1–231. [PubMed] [Google Scholar]
  14. Hellman B., Idahl L. A., Lernmark A., Sehlin J., Täljedal I. B. Stimulation of insulin release by thiols. Biochim Biophys Acta. 1975 May 5;392(1):101–109. doi: 10.1016/0304-4165(75)90170-1. [DOI] [PubMed] [Google Scholar]
  15. Huber A. M., Gershoff S. N. Effect of zinc deficiency in rats on insulin release from the pancreas. J Nutr. 1973 Dec;103(12):1739–1744. doi: 10.1093/jn/103.12.1739. [DOI] [PubMed] [Google Scholar]
  16. Ithakissios D. S., Ghafghazi T., Mennear J. H., Kessler W. V. Effect of multiple doses of cadmium on glucose metabolism and insulin secretion in the rat. Toxicol Appl Pharmacol. 1975 Jan;31(1):143–149. doi: 10.1016/0041-008x(75)90062-9. [DOI] [PubMed] [Google Scholar]
  17. LOWRY J. R., BALDWIN R. R., HARRINGTON R. V. Uptake of radiozinc by normal and diabetic rat pancreas. Science. 1954 Feb 12;119(3085):219–220. doi: 10.1126/science.119.3085.219. [DOI] [PubMed] [Google Scholar]
  18. Menahan L. A., Wieland O. Glucagon-like action of N6,2'-O-dibutyryl cyclic 3',5'-AMP on perfused rat liver. Biochem Biophys Res Commun. 1967 Dec 29;29(6):880–885. doi: 10.1016/0006-291x(67)90303-8. [DOI] [PubMed] [Google Scholar]
  19. Merali Z., Singhal R. L. Protective effect of selenium on certain hepatotoxic and pancreotoxic manifestations of subacute cadmium administration. J Pharmacol Exp Ther. 1975 Oct;195(1):58–66. [PubMed] [Google Scholar]
  20. Murata I., Hirono T., Saeki Y., Nakagawa S. Cadmium enteropathy, renal osteomalacia ("Itai Itai" disease in Japan). Bull Soc Int Chir. 1970 Jan-Feb;29(1):34–42. [PubMed] [Google Scholar]
  21. PARIZEK J. The destructive effect of cadmium ion on testicular tissue and its prevention by zinc. J Endocrinol. 1957 Apr;15(1):56–63. doi: 10.1677/joe.0.0150056. [DOI] [PubMed] [Google Scholar]
  22. SCHROEDER H. A., BALASSA J. J. Abnormal trace metals in man: cadmium. J Chronic Dis. 1961 Aug;14:236–258. doi: 10.1016/0021-9681(61)90156-4. [DOI] [PubMed] [Google Scholar]
  23. SUTHERLAND E. W., RALL T. W., MENON T. Adenyl cylase. I. Distribution, preparation, and properties. J Biol Chem. 1962 Apr;237:1220–1227. [PubMed] [Google Scholar]
  24. Singhal R. L., Merali Z., Kacew S., Sutherland D. J. Persistence of cadmium-induced metabolic changes in liver and kidney. Science. 1974 Mar 15;183(4129):1094–1096. doi: 10.1126/science.183.4129.1094. [DOI] [PubMed] [Google Scholar]
  25. Stowe H. D., Wilson M., Goyer R. A. Clinical and morphologic effects of oral cadmium toxicity in rabbits. Arch Pathol. 1972 Nov;94(5):389–405. [PubMed] [Google Scholar]
  26. Sutherland E. W., Robison G. A. The role of cyclic AMP in the control of carbohydrate metabolism. Diabetes. 1969 Dec;18(12):797–819. doi: 10.2337/diab.18.12.797. [DOI] [PubMed] [Google Scholar]
  27. Walaas O., Walaas E., Gronnerod O. Molecular events in the action of insulin on cell metabolism. The significance of cyclic AMP dependent protein kinases. Acta Endocrinol Suppl (Copenh) 1974;191:93–129. doi: 10.1530/acta.0.077s0093. [DOI] [PubMed] [Google Scholar]
  28. Watkins D. T., Moore M. Effect of sulfhydryl-binding reagents on insulin release from isolated secretion granules. Endocrinology. 1974 Aug;95(2):485–491. doi: 10.1210/endo-95-2-485. [DOI] [PubMed] [Google Scholar]
  29. Watkins D., Cooperstein S. J., Lazarow A. Effect of sulfhydryl reagents on permeability of toadfish islet tissue. Am J Physiol. 1970 Aug;219(2):503–509. doi: 10.1152/ajplegacy.1970.219.2.503. [DOI] [PubMed] [Google Scholar]
  30. Wicks W. D. Induction of hepatic enzymes by adenosine 3',5'-monophosphate in organ culture. J Biol Chem. 1969 Jul 25;244(14):3941–3950. [PubMed] [Google Scholar]

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

RESOURCES