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Am J Physiol Endocrinol Metab 273: E1090-E1101, 1997;
0193-1849/97 $5.00
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Vol. 273, Issue 6, E1090-E1101, December 1997

Insulinotropic action of alpha -D-glucose pentaacetate: functional aspects

Willy J. Malaisse, Carmen Sánchez-Soto, M. Elena Larrieta, Marcia Hiriart, Hassan Jijakli, Concepción Viñambres, María L. Villanueva-Peñacarrillo, Isabel Valverde, Ole Kirk, Marcel M. Kadiata, and Abdullah Sener

Laboratory of Experimental Medicine, Brussels Free University, B-1070 Brussels, Belgium; Department of Biophysics, Institute of Cellular Physiology, Universidad Nacional Autónoma de México, Mexico City, DF-04510 Mexico City, Mexico; Fundación Jiménez Díaz, 28040 Madrid, Spain; and Novo Nordisk, DK-2880 Bagsvaerd, Denmark

The functional determinants of the insulinotropic action of alpha -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 86Rb outflow, and augmenting 45Ca efflux from prelabeled islets. The secretory response to the ester was suppressed in the absence of Ca2+ 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, alpha -D-galactose pentaacetate, and beta -D-galactose pentaacetate all failed to stimulate insulin release. The secretory response to alpha -D-glucose pentaacetate was reproduced by beta -D-glucose pentaacetate and, to a lesser extent, by beta -L-glucose pentaacetate. It differed from that evoked by unesterified D-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 alpha -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.

pancreatic islets; insulin release


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