The effects of barbituric acid and 5-nitro barbituric acid on glycemic responses and in vitro insulin release in mice
Wright, G.A.; Spratto, G.R.; Mennear, J.H.
Toxicology and Applied Pharmacology 50(2): 189-198
1979
ISSN/ISBN: 0041-008X PMID: 388723 Document Number: 140790
The effects of barbituric acid (BA) and 5-nitro BA on carbohydrate metabolism were assessed in mice. The administration of BA or the 5-nitro analog elicited an initial hyperglycemia, glucose intolerance and a decrease in responsiveness to tolbutamide. The glycemic responses produced by 5-nitro BA administration appeared greater than those elicited by the parent compound, these effects were abolished when the analog was administered to fasted or adrenalectomized mice. 5-Nitro BA did not inhibit D-glucose-stimulated insulin secretion in vitro. BA attenuated both D-glucose- and tolbutamide-induced insulin release from isolated pancreatic islets. A competition for pancreatic .beta. cell binding sites is offered as the possible mechanism of antagonism between BA and the sulfonylurea. BA exerts its effects on carbohydrate metabolism directly on the pancreas but the effects of the 5-nitro analog appear to be mediated through stress-related factors. Due to its specificity for the insulin-secreting pancreatic .beta. cells, structure-activity relationship studies with BA are likely to augment the development of a compound which will find clinical utility in the management of hyperinsulinism.