Insulin secretagogues bind to the so-called SU-receptors, which is a subunit of the voltage-dependent potassium adenosine triphosphate (KATP) channels on beta cells. Upon closure of those channels with subsequent inhibition of the efflux of potassium ions from the resting beta cell, the cell membrane is depolarized and voltage-dependent calcium channels are opened. The calcium entry into the cell leads to contraction of microtubules and thereby insulin exocytosis from vesicles, that is insulin secretion [10,22,23]. Thus, SUs induce insulin secretion at lower plasma glucose thresholds as normal. When given in maximally effective doses (Table 1), all available SUs seem to have equipo-tent capacity for stimulation of insulin secretion and lowering plasma glucose [24-27]. Similar results were obtained from the UKPDS comparing first- and second-generation SUs [11,12].
Glinides induce insulin secretion similarly (closure of the KATP channels), but they bind to the sulfony-lurea receptor at a different site and with different kinetics . Unlike conventional sulphonylureas, they are not internalized within the beta cell and have less stimulatory effect during postabsorptive conditions. Therefore, the risk of severe hypoglycaemic episodes has been shown to be markedly less than with classical SUs [28,29].
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