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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Direct in vitro effect of a sulfonylurea to increase human fibroblast insulin receptors.

We have studied the effects of the oral sulfonylurea agent glyburide to modulate insulin receptors on nontransformed human fibroblasts in tissue culture. When glyburide was added to monolayers of human fibroblasts, a dose-dependent increase in the number of cell surface receptors was observed with a maximum effect (19% increase) seen at 1 microgram/ml glyburide. Insulin can induce a loss of insulin receptors in these cells, and when fibroblasts are exposed to 100 ng/ml insulin for 6 h, approximately 60% of the initial complement of cell surface receptors are lost. When the process of insulin-induced receptor loss (or down regulation) was studied in the presence of glyburide, the drug exerted a marked inhibitory effect on this regulatory process. Thus, glyburide inhibited insulin-induced receptor loss in a dose-dependent fashion, and the maximally effective drug concentration (1 microgram/ml) inhibited 34% of the receptor loss. These studies demonstrate a direct in vitro effect of this oral hypoglycemic agent to increase the number of cell surface insulin receptors or prevent their loss, presumably by slowing the rate of receptor internalization. These findings may explain the well known extrapancreatic effect of sulfonylurea agents to improve insulin-mediated tissue glucose metabolism.[1]

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