Subcellular Compartmentation and Degradation of Insulin in Liver at the Outset of Hypoglycaemia Induced by Oral Antidiabetic Sulphanylureas

Abstract

It is now well documented that glibenclamide and possibly most of the other sulphanylureas reduce blood glucose content, mainly by stimulating the release of insulin in the pancreas (1). The primary receptor for glibenclamide may be in the pancreas, however, no significant interaction between Langerhans Islets and ³H- or ¹⁴C-glibenclamide was observed. The rapidly induced macromolecular synthesis resulting in an increase in the size of the nuclei of β-cells within a few hours following the administration of sulphanylureas (2) suggests that some extra-pancretic ‚trophic‘ influence on the β-cells may be operating. It appears that a specific direct inhibition of macromolecular synthesis in the β-cells by preformed insulin molecules is unlikely for following administration of sulphanylureas, in addition to release of insulin, both α-and β-cells hypertrophize (3). The pituitary gland has possibly no role in the effect of sulphanylureas (4). Furthermore, various effects on fat tissue or glucose utilization also indicate a more complex effect than would be explainable simply in terms of stimulated insulin secretion. Analysis of various in vivo effects of glibenclamide together with the observation that the liver accumulates the highest amount of glibenclamide indicate the presence of some receptors inside the liver cell in spite of the report that sulphanylureas are distributed in the extracellular space (5).