alexa Glibenclamide: an old drug with a novel mechanism of action?
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Diabetic Complications & Medicine

Author(s): L Luzi

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This review is meant to give to the readers an overview of the pharmacokinetics, pharmacodinamics, mechanism(s) of action and therapeutical indications of the sulfonylurea compound glibenclamide, which is a cardinal drug in the treatment of type 2 diabetes mellitus. Data produced in our own laboratory over the past 15 years will be presented, along with reference to the main literature in the field. As pharmacokinetics is concerned, special emphasis will be placed on the detrimental effect of hyperglycemia in the intestinal absorption of this class of drugs. Both β-cell and extrapancreatic effects of glibenclamide will be highlighted. The mechanism of action of the drug consists in the inhibition of the ATP-sensitive K+ channels, which leads to depolarization of the cells and insulin secretion. Based on the same mechanism are also the extrapancreatic action of the drug at the liver, skeletal muscle, heart muscle and smooth muscle sites. The newly discovered possible physiological actions of the C-peptide molecule [suggesting a stimulatory effect of C-peptide on the Na+, K+ (ATPase) pump and on diabetic complications], cast a new light on all therapeutic approaches (like sulfonylurea class of compounds and whole pancreas or islet of Langerhans transplantation), which induce/replace both insulin and C-peptide secretion.

This article was published in Acta Diabetologica and referenced in Journal of Diabetic Complications & Medicine

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