Insulinotropic action of formycin A.
The adenosine analogue formycin A is phosphorylated to its triphosphate ester in a sequence of reactions catalyzed by adenosine kinase and adenylate kinase. Formycin A triphosphate is an ATP analogue that is currently used to probe for ATP binding sites. Considering the key role ascribed to ATP in the coupling of metabolic to cationic events in the process of glucose-stimulated insulin release, we investigated whether formycin A displays insulinotropic action in rat pancreatic islets. Formycin A (10 microM to 1.0 mM) caused a concentration-related increase of insulin release evoked by 8.3 mM D-glucose and prevented the fall in insulin output otherwise observed over two successive incubations of 90 min each. Formycin A (1.0 mM) also augmented insulin secretion at low (5.6 mM) and high (16.7 mM) concentrations of D-glucose. At the low hexose concentration, the secretory response to formycin A was comparable to that evoked by either glibenclamide or glipizide. At higher concentrations of D-glucose, however, formycin A was more potent than the hypoglycemic sulfonylureas in enhancing insulin output. These findings support the role of ATP in glucose-stimulated insulin release and, therefore, suggest that ATP mimetics represent a new class of insulinotropic agents that have potential utility in the treatment of non-insulin-dependent diabetes mellitus.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
W J
WJ
Malaisse
A
A
Sener
H E
HE
Gruber
M D
MD
Erion
D000818:Animals; D005260:Female; D005573:Formycins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology
D005573:Formycins; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C034550:formycin; D005947:Glucose