Insulinotropic action of (-d-glucose pentaacetate : functional
aspects.
Malaisse, Willy J., Carmen Sanchez-Soto, M. Elena Larrieta, Marcia
Hiriart, Hassan Jijakli, Concepcin Viambres, Mara L. Villanueva
-Peacarrillo, 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 Autnoma de M[theta]xico,
Mexico City, DF-04510 Mexico City, Mexico; Fundacin Jimonez Daz,
28040 Madrid, Spain; and Novo Nordisk A/S, DK-2880 Bagsvaerd,
Denmark
APStracts 4:0191E, 1997.
The functional determinants of the insulinotropic action of (-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 prelabelled 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 little role in its insulinotropic action. Thus,
acetate, methyl acetate, ethyl acetate, (-D-galactose pentaacetate
and -D-galactose pentaacetate all failed to stimulate insulin
release. The secretory response to (-D-glucose pentaacetate was
reproduced by -D-glucose pentaacetate and, to a lesser extent, by -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 (-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.
Received 11 June 1997; accepted in final form 20 August 1997.
APS Manuscript Number E272-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 September 1997