Summary
The effects of four sulphonylureas (gliclazide, glibenclamide, chlorpropamide and glipizide) on insulin binding and insulin action were studied in vitro using primary cultured rat hepatocytes. Cells were cultured for 20 h in the absence or presence of the sulphonylurea. The binding of insulin to rat hepatocyte monolayers was not altered in cells previously exposed to gliclazide at 0.7, 7.0 or 70 μg/ml; and to glibenclamide, chlorpropamide, or glipizide at 0.1, 1.0 and 10 μg/ ml. Insulin-induced down regulation was not affected by a simultaneous exposure of hepatocyte monolayers to any of the four agents. The stimulatory effect of insulin on α-aminoisobutyric acid uptake by the cells was not modified following exposure to the drugs. These studies indicate that the sulphonylureas tested do not have a direct effect on insulin receptors in hepatocytes; and that, in vitro, they do not alter the post-receptor events involved in the insulin-induced stimulation of amino acid transport in these cells.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Olefsky JM, Reaven GM (1976) Effects of sulfonylurea therapy on insulin binding to mononuclear leukocytes of diabetic patients. Am J Med 60: 89–95
Feinglos MN, Lebovitz HE (1978) Sulfonylureas increase the number of insulin receptors. Nature 276: 184–185
Bachmann W, Bottger I, Haslbeck M, Mehnert H (1979) Extrapancreatic action of sulfonylureas: effect of gliquidone on insulin and glucagon binding to rat liver plasma membranes. Eur J Clin Invest 9: 411–415
Beck-Nielsen H, Pedersen O, Lindskov MO (1979) Increased insulin sensitivity and cellular binding in obese diabetics following treatment with glibenclamide. Acta Endocrinol 90: 451–462
Prince MJ, Olefsky JM (1980) Direct in vitro effect of a sulfonylurea to increase human fibroblast insulin receptors. J Clin Invest 66: 608–611
Maloff BL, Lockwood DH (1981) In vitro effects of a sulfonylurea on insulin action in adipocytes. J Clin Invest 68: 85–90
Morin O, Fehlmann M, Freychet P (1982) Binding and action of insulin and glucagon in monolayer cultures and fresh suspensions of rat hepatocytes. Mol Cell Endocrinol 25: 339–352
Freychet P (1976) Insulin receptors. In: Blecher M (ed) Methods in receptor research, Part II. Marcel Dekker, New York, Basel, pp 385–428
Fehlmann M, Le Marchand-Brustel Y, Dolais-Kitabgi J, Morin O, Freychet P (1981) Biological activity and receptor binding properties of biosynthetic human insulin in isolated rat hepatocytes and mouse soleus muscle in vitro. Diabetes Care 4: 223–227
Dolais-Kitabgi J, Checler F, Rey JF, Morin O, Freychet P (1981) Insulin stimulation of amino acid transport in primary cultured rat hepatocytes varies in direct proportion to insulin binding. FEBS Lett 128: 321–324
Fehlmann M, Morin O, Kitabgi P, Freychet P (1981) Insulin and glucagon receptors of isolated rat hepatocytes: comparison between hormone binding and amino acid transport stimulation. Endocrinology 109: 253–261
Vigneri R (1982) Comparison of the in vitro effect of biguanides and sulfonylureas on insulin binding to its receptor in target cells. J Cell Endocrinol Metab 54: 95–100
Colwell AR (1964) Potentiation of insulin action on the liver by tolbutamide. Metabolism 13: 1310–1317
Lebovitz HE, Feinglos MN, Bucholtz HK, Lebovitz FL (1977) Potentiation of insulin action: a probable mechanism for the antidiabetic action of sulfonylurea drugs. J Clin Endocrinol Metab 45: 601–604
Putnam WS, Andersen DK, Jones RS, Lebovitz AF (1981) Selective potentiation of insulin mediated glucose disposal in normal dogs by the sulfonylurea glipizide. J Clin Invest 4: 1016–1023
Blumenthal SA (1977) Potentiation of the hepatic action of insulin by chlorpropamide. Diabetes 26: 485–489
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dolais-Kitabgi, J., Alengrin, F. & Freychet, P. Sulphonylureas in vitro do not alter insulin binding or insulin effect on amino acid transport in rat hepatocytes. Diabetologia 24, 441–444 (1983). https://doi.org/10.1007/BF00257344
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00257344