Mode of Action of Sulfonylureas

  • U. Panten
  • M. Schwanstecher
  • C. Schwanstecher
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 119)


Both pancreatic and extrapancreatic effects have been suggested to contribute to the therapeutic benefit of sulfonylureas for type II diabetic patients. Clear evidence for stimulation of insulin secretion by sulfonylureas has been presented (Loubatières 1957a, b; Yalow et al. 1960; Bouman and Gaarenstrom 1961; Coore and Randle 1964; Malaisse et al. 1967). On the other hand, sulfonylurea-induced extrapancreatic effects observed in clinical studies may have been consequences of an increase in insulin secretion (Gerich 1989; Melander et al. 1989). This view is not invalidated by the numerous in vitro investigations demonstrating direct effects of sulfonylureas on metabolism of extrapancreatic cells (for a review see Beck-Nielsen et al. 1988). Most of the latter effects occurred at free (non-protein-bound) sulfonylurea concentrations well beyond those measured in the plasma from treated patients (for references see Panten et al. 1989). In the plasma, sulfonylureas are highly protein bound, e.g., 6% of tolbutamide and less than 1% of glibenclamide are free. The free proportions of sulfonylureas easily cross capillary walls (perhaps with the exception of the blood-brain barrier capillaries) for the following reasons: Firstly, due to their high lipid solubility sulfonylureas rapidly penetrate membranes (Panten et al. 1989). Secondly, fenestrated endothelia (e.g., in pancreatic islets) are no barriers for sulfonylureas (M r < 500).


KATP Channel Sulfonylurea Receptor Hypoglycemic Sulfonylurea Glibenclamide Binding Stimulatory Nucleotide 
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© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • U. Panten
  • M. Schwanstecher
  • C. Schwanstecher

There are no affiliations available

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