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Insulinotropic action of formycin A
W J Malaisse1, A Sener, H E Gruber
1Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Abstract:
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.
Insights
Formycin A, an ATP analogue, stimulates insulin release from rat pancreatic islets, suggesting its potential as a novel therapeutic for diabetes.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Adenosine triphosphate (ATP) is crucial for glucose-stimulated insulin release.
- Formycin A is an ATP analogue used to study ATP binding sites.
Purpose of the Study:
- To investigate if formycin A has insulinotropic action in rat pancreatic islets.
- To explore ATP mimetics as potential diabetes treatments.
Main Methods:
- Rat pancreatic islets were treated with varying concentrations of formycin A.
- Insulin release was measured under different glucose concentrations.
- Formycin A's effects were compared to sulfonylureas like glibenclamide and glipizide.
Main Results:
- Formycin A increased insulin release in a dose-dependent manner, particularly at 8.3 mM D-glucose.
- It maintained insulin output over prolonged incubation periods.
- Formycin A enhanced insulin secretion at both low (5.6 mM) and high (16.7 mM) glucose levels, outperforming sulfonylureas at higher glucose concentrations.
Conclusions:
- Findings support ATP's role in glucose-stimulated insulin release.
- ATP mimetics, like formycin A, represent a new class of insulinotropic agents.
- These agents show potential for treating non-insulin-dependent diabetes mellitus.