Insulinotropic action of α-d-glucose pentaacetate: functional aspects

• Published in: American journal of physiology: endocrinology and metabolism 1997-12, Vol.273 (6), p.E1090
• Main Authors: Malaisse, Willy J, Sánchez-Soto, Carmen, Larrieta, M Elena, Hiriart, Marcia, Jijakli, Hassan, Viñambres, Concepción, Villanueva-Peñacarrillo, María L, Valverde, Isabel, Kirk, Ole, Kadiata, Marcel M, Sener, Abdullah
• Format: Article
• Language: English
• ISSN: 1522-1555
• DOI: 10.1152/ajpendo.1997.273.6.E1090

The functional determinants of the insulinotropic action of α-d-glucose pentaacetate were investigated in rat pancreatic islets. The ester mimicked the effect of nutrient secretagogues by recruiting individual B cells into an active secretory state, stimulating proinsulin biosynthesis, inhibiting Rb outflow, and augmenting Ca efflux from prelabeled islets. The secretory response to the ester was suppressed in the absence of Ca and potentiated by theophylline or cytochalasin B. The generation of acetate from the ester apparently played a small role in its insulinotropic action. Thus acetate, methyl acetate, ethyl acetate, α-d-galactose pentaacetate, and β-d-galactose pentaacetate all failed to stimulate insulin release. The secretory response to α-d-glucose pentaacetate was reproduced by β-d-glucose pentaacetate and, to a lesser extent, by β-l-glucose pentaacetate. It differed from that evoked by unesterifiedd-glucose by its resistance to 3- O-methyl-d-glucose,d-mannoheptulose, and 2-deoxy-d-glucose. It is concluded that the insulinotropic action of α-d-glucose pentaacetate, although linked to the generation of the hexose from its ester, entails a coupling mechanism that is not identical to that currently implied in the process of glucose-induced insulin release.