They are bound to the sulfonylurea receptor of the pancreatic b-cell membrane and cause secretion of insulin. The binding occurs at a different part of the receptor compared to sulfonylureas, but as with sulfonylureas, closing of the potassium channels follows, with a subsequent depolarization of the membrane, opening up of calcium channels and entry of calcium ions into the cell. The increased intracellular calcium ions concentration ultimately causes the mobilization of the secretory insulin granules towards the cell membrane and the exit of insulin. The effect of meglitinides restores to some degree the first phase of insulin secretion.
Their action depends on glucose levels. It is interrupted when these are low, and therefore the hypoglycaemias sometimes caused by the action of sulfonylureas, which is prolonged and independent from the glucose levels, are avoided. The action of meglitinides begins after 20-40 minutes and lasts roughly 3-4 hours (nateglinide has the quickest and shortest action of all insulin-secretagogues). There are no data concerning the effect of meglitinides on serum lipids.
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