Summary
The cellular mechanism(s) by which the biguanide, metformin, exerts its antihyperglycaemic effect was investigated. Rat adipocytes were either treated acutely (2 h) or maintained in a biochemically defined medium (20 h) in the presence or absence of metformin (1 x 10−4 mol/1). Exposure to the drug resulted in a significant enhancement (p < 0.01) of hexose transport in both the absence (basal) and presence of insulin. Stimulation of transport was not explained by the increase in the basal state alone, since the incremental response to maximally effective concentrations of insulin was significantly enhancedp<0.025. Insulin-receptor tyrosine kinase activity was examined under the same experimental conditions. Activity of the kinase was unaltered as evaluated by phosphorylation of an artificial substrate and by phosphorylation of the receptor in situ. Furthermore, in this investigation neither insulin receptor number nor affinity was changed in adipose tissue treated with metformin. These studies indicate that metformin potentiates the effect of insulin on glucose transport at a site(s) beyond insulin receptor binding and phosphorylation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hermann, LS (1979) Metformin: a review of its pharmacological properties and therapeutic use. Diabetes Metab 5: 233–245
Vigneri R, Pezzino V, Wong KY, Goldfine ID (1982) Comparison of the in vitro effects of biguanides and sulfonylureas on insulin binding to its receptor in target cells. J Clin Endocrinol Metab 54: 95–100
Cigolini M, Bosello O, Zancanaro C, Orlandi PG, Fezzi O, Smith U (1984) Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro. Diabete Metabolisme 10: 311–315
Lord JM, Puah JA, Atkins TW, Bailey CJ (1985) Postreceptor effect of metformin on insulin action in mice. J Pharm Pharmacol 37: 821–823
Cobb MH, Rosen OM (1984) The insulin receptor and tyrosine protein kinase activity. Biochim Biophys Acta 738: 1–8
Maloff BL, Lockwood DH (1981) In vitro effects of a sulfonylurea on insulin action in adipocytes. J Clin Invest 68: 85–90
Hayes GR, Lockwood DH (1986) The role of cell surface sialic acid in insulin receptor function and insulin action. J Biol Chem 261: 2791–2798
Hayes GR, Lockwood DH (1986) Stimulation of insulin receptor (IR) phosporylation by H2O2 in intact adipocytes. Diabetes 35 [Suppl 1]: 2A
Arsenis G, Livingston JN (1986) Alterations in the tyrosine kinase activity of the insulin receptor produced by in vitro hyperinsulinemia. J Biol Chem 261: 147–153
LeMarchand-Brustel Y, Gremeaux T, Ballotti R, Van Obberghen E (1985) Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice. Nature 315: 676–679
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jacobs, D.B., Hayes, G.R., Truglia, J.A. et al. Effects of metformin on insulin receptor tyrosine kinase activity in rat adipocytes. Diabetologia 29, 798–801 (1986). https://doi.org/10.1007/BF00873219
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00873219