Abstract
POSSIBLE schemes for the mechanism of the hypoglycaemic action of biguanides have raised considerable controversy in recent years. The possibility that these drugs may act through inhibition of oxidative phosphorylation, which may increase the glucose uptake of peripheral tissues1, has been frequently emphasized2–5, but experiments on the kinetics of glucose loads6 as well as the demonstration that no correlation exists between the hypoglycaemic effect of various biguanides and their inhibitory action on oxidative phosphorylations7,8 did not support this hypothesis. Moreover, it is now well established that the biguanide drugs have no effect on the glycaemia of normal animals and men, and that their action is restricted to the diabetic and fasting animal. Thus it appeared reasonable to assume that they may interfere with one or more metabolic pathways which are widely different in the normal and diabetic organism. One of these is the gluconeogenetic pathway, resulting in the synthesis of glucose from metabolites containing three or four carbon atoms, including amino-acids. The possibility that such a mechanism may explain the anti-diabetic action of at least two biguanides (phenylethylbiguanide (PEBG) and dimethylbiguanide (DMBG)) has been investigated.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Randle, P. J., and Smith, G. H., Biochem. J., 70, 490 (1958).
Steiner, D. F., and Williams, R. H., Biochim. Biophys. Acta, 30, 329 (1958).
Clarke, D. W., and Forbath, N., Diabetes, 9, 167 (1960).
Wick, A. N., Larson, E. R., and Sfrif, G. S., J. Biol. Chem., 233, 296 (1958).
Fajans, S. S., Moorhouse, J. A., Doorenbos, H., Louis, L. H., and Conn, J. W., Clin. Res., 6, 252 (1958).
Fajana, S. S., Moorhouse, J. A., Doorenbos, H., Lawrence, H. L., and Conn, J. W., Diabetes, 9, 194 (1960).
Meyer, F., C.R. Acad. Sci., Paris, 251, 1928 (1960).
Ungar, G., Psychoyos, S., and Hall, H. A., Metabolism, 9, 36 (1960).
Good, C. A., Kramer, H., and Somogyi, M., J. Biol. Chem., 100, 485 (1933).
Hugget, A. St. G., and Nixon, D. A., Lancet, ii, 368 (1957).
Moore, S., and Stein, W. H., J. Biol. Chem., 211, 907 (1954).
Krebs, H. A., Bennett, D. A. H., Gasquet, P., Gascoyne, T., and Yoshida, T., Biochem. J., 86, 22 (1963).
Ungar, G., Freedman, L., and Shapiro, S. L., Proc. Soc. Exp. Biol. Med., 95, 190 (1957).
Weber, G., Singhal, R. L., Stamm, N. B., Fisher, E. A., and Mentendiek, M. A., Advances in Enzyme Regulation, 2, 2 (1964).
Williams, R. H., Tybergheim, J. M., Hyde, P. M., and Nielsen, R. L., Metabolism, 6, 311 (1957).
Utter, M. F., and Keech, D. B., J. Biol. Chem., 238, 2603, 2609 (1963).
Kun, E., Ayling, J. E., and Baltimore, B. G., J. Biol. Chem., 239, 896 (1964).
Shrago, E., and Lardy, H. A., J. Biol. Chem., 241, 663 (1966).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
MEYER, F., IPAKTCHI, M. & CLAUSER, H. Specific Inhibition of Gluconeogenesis by Biguanides. Nature 213, 203–204 (1967). https://doi.org/10.1038/213203a0
Issue Date:
DOI: https://doi.org/10.1038/213203a0
- Springer Nature Limited
This article is cited by
-
Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer
Scientific Reports (2016)
-
Molecular mechanism of action of metformin: old or new insights?
Diabetologia (2013)
-
Moleculair werkingsmechanisme van metformine: oude of nieuwe inzichten?
Nederlands Tijdschrift voor Diabetologie (2013)
-
Insulin resistance/hyperinsulinemia and reproductive disorders in infertile women
Reproductive Medicine and Biology (2010)
-
Decreased skeletal muscle phosphotyrosine phosphatase (PTPase) activity towards insulin receptors in insulin-resistant Zucker rats measured by delayed Europium fluorescence
Diabetologia (1996)