Dual actions of sulfonylureas and glyburide. Receptor and post-receptor effects.
Glyburide and other sulfonylureas consistently enhance receptor binding in cells from patients with non-insulin-dependent diabetes mellitus, whereas no effects and mixed effects have been demonstrated in cells from patients with insulin-dependent diabetes mellitus and in normal cells, respectively. These findings indicate that the experimental model may be critical in demonstrating sulfonylurea effects on receptor binding. Postbinding function studies have shown a definite enhancement of peripheral glucose metabolism by sulfonylurea drugs; such post-receptor changes have not clearly correlated with receptor binding alterations. Studies using mouse-cultured myocytes indicate that both glyburide and tolazamide have stimulatory effects on glucose uptake, whereas only glyburide caused an increase in receptor binding. The data suggest a major and widespread post-receptor function for the sulfonylurea drugs, particularly glyburide, possibly mediated through pathways similar but not identical to insulin pathways. The direct receptor effects, in contrast, are possibly more tissue-specific and/or disease-dependent. In non-insulin-dependent diabetes mellitus, these drugs exert clinical efficacy by acting through both mechanisms.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005347:Fibroblasts / Q000378:metabolism; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014042:Tolazamide / Q000627:therapeutic use
D007328:Insulin; D013453:Sulfonylurea Compounds; D014042:Tolazamide; D011972:Receptor, Insulin; D005905:Glyburide