The riddle of formycin A insulinotropic action
| Autor: | María Luisa Villanueva-Peñacarrillo, Philippe Lebrun, P D Van Poelje, Patrik Rorsman, Isabel Valverde, Bernard Pirotte, Willy Malaisse, J Gabel, Concepción Viñambres |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Bisindolylmaleimide Adenosine Adenosine kinase Biology In Vitro Techniques Biochemistry Tubercidin chemistry.chemical_compound Islets of Langerhans Internal medicine Glyburide Insulin Secretion medicine Diazoxide Animals Insulin Protein kinase C Forskolin Pancreatic islets Ribonucleotides Adenosine receptor Rats Endocrinology medicine.anatomical_structure Glucose Mechanism of action chemistry Diabetes Mellitus Type 2 Verapamil Xanthines biology.protein Calcium Female medicine.symptom Formycins medicine.drug |
| Zdroj: | Biochemical and molecular medicine. 57(1) |
| ISSN: | 1077-3150 |
| Popis: | Formycin A augments insulin release evoked by glucose (5.6 mm or more), this effect not being rapidly reversible. The mechanism responsible for the insulinotropic action of formycin A was investigated in isolated pancreatic islets. It could not be ascribed to facilitation of glucose metabolism. On the contrary, formycin A inhibited glucose oxidation, lowered ATP content, and impaired glucose-stimulated protein biosynthesis. The insulinotropic action of formycin A was apparently attributable to its conversion to formycin A 5'-triphosphate, both this process and the secretory response to formycin A being abolished by the inhibitor of adenosine kinase 5-iodotubercidin. In agreement with the latter view, adenosine receptor antagonists such as 8-cyclopentyl-1, 3-dipropylxanthine and 3,7-dimethyl-1-propargylxanthine failed to suppress and, instead, augmented the insulinotropic action of formycin A. Unexpectedly, however, formycin A failed to decrease 86Rb efflux, this coinciding with a low efficiency of formycin A 5'-triphosphate to inhibit KATP-channel activity in excised membranes and with the fact that formycin A increased gliben-clamide-stimulated insulin release. The secretory response to formycin A represented a Ca2+-dependent process suppressed in the absence of extracellular Ca2+ or presence of verapamil and associated with an increased net uptake of 45Ca. Nevertheless, the view that formycin A exerts any major effect upon intracellular Ca2+ redistribution, protein kinase C activity, or cyclic AMP net production also met with objections such as the minor secretory effect of formycin A in islets exposed to a high concentration of K+ in the presence of a diazoxide analog, the resistance of formycin A insulinotropic action to bisindolylmaleimide, the poor increase of cyclic AMP content in formycin A-stimulated islets, and the pronounced enhancement by forskolin or theophylline of insulin release from islets exposed to formycin A. It is concluded, therefore, that the mechanism of action of formycin A in the pancreatic beta-cell remains to be elucidated. |
| Databáze: | OpenAIRE |
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