1.Inhibition of insulin release by alpha- and beta-D-galactose pentaacetate.
Malaisse WJ1, Kadiata MM. Int J Mol Med. 1998 Sep;2(3):331-2.
Several monosaccharide polyacetate esters display higher biological efficiency than the corresponding unesterified carbohydrates, this being attributable to their capacity to cross the plasma membrane without requiring the intervention of a specific carrier system and to their subsequent intracellular esterase-catalyzed hydrolysis. Some of these esters, however, also exert a direct effect upon a receptor system apparently displaying analogies with that involved in the identification of bitter compounds by taste buds. For instance, under suitable experimental conditions, esters of non-nutrient monosaccharides, such as L-glucose, D-mannoheptulose or 2-deoxy-D-glucose, unexpectedly stimulate insulin release. The present work reveals that alpha-D-galactose pentaacetate and, to a lesser extent, beta-D-galactose pentaacetate both inhibit leucine-induced insulin release in rat pancreatic islets. This indicates that the postulated receptor system displays anomeric specificity and may participate in a negative modulation of insulin secretion.
2.Insulinotropic action of the polyacetate esters of metabolized and non-metabolized monosaccharides in pancreatic islets from normal and diabetic rats.
Malaisse WJ1, Laghmich A, Ladrière L, Kadiata MM, Sener A. Res Commun Mol Pathol Pharmacol. 1998 Jan;99(1):81-92.
The polyacetate esters of selected monosaccharides were recently found to either stimulate insulin release or inhibit glucose-stimulated insulin secretion in islets from normal rats. The present study extends such findings both to new combinations of either D-glucose or L-leucine and some polyacetate esters and to hereditarily diabetic, as distinct from normal, rats. In the normal animals, 2-deoxy-D-glucose tetraacetate (1.7 mM) increased both glucose- and leucine-stimulated insulin output. The secretory response to L-leucine was also increased by beta-D-glucose pentaacetate, but inhibited by alpha-D-galactose pentaacetate and D-mannoheptulose hexaacetate (1.7 mM) in the islets of normal rats. In the diabetic rats, the secretory response to D-glucose (8.3 mM) was increased by alpha- or beta-D-glucose pentaacetate and 2-deoxy-D-glucose tetraacetate (1.7 mM), inhibited by alpha-D-galactose pentaacetate and D-mannoheptulose hexaacetate, and unaffected by beta-L-glucose pentaacetate, all esters being tested at 1.
3.Bitter taste of monosaccharide pentaacetate esters.
Malaisse WJ1, Malaisse-Lagae F. Biochem Mol Biol Int. 1997 Dec;43(6):1367-71.
The pentaacetate esters of several, but not all, monosaccharides were recently found to stimulate insulin release from rat pancreatic islets. We have now compared the taste of solutions of either these esters or the corresponding unesterified monosaccharides. The sweet taste of the latter monosaccharides (0.22 M) ranged as follows: D-glucose approximately or = D-galactose approximately or = D-mannoheptulose > L-glucose. None of the esters (1.7 mM) displayed a sweet taste. However, the alpha- and beta-anomer of D-glucose pentaacetate, the alpha-anomer of D-mannose pentaacetate and the beta-anomer of L-glucose pentaacetate all displayed a bitter taste, whilst both alpha- and beta-D-galactose pentaacetate yielded doubtful results. Since such a situation is comparable to that characterizing the islet B-cell response to these esters, it is proposed that the intracellular interaction between the esters or their hydrolytic products and a protein involved in the recognition of bitter taste in taste buds may participate in their insulinotropic action.
4.Insulinotropic action of alpha-D-glucose pentaacetate: functional aspects.
Malaisse WJ1, Sánchez-Soto C, Larrieta ME, Hiriart M, Jijakli H, Viñambres C, Villanueva-Peñacarrillo ML, Valverde I, Kirk O, Kadiata MM, Sener A. Am J Physiol. 1997 Dec;273(6 Pt 1):E1090-101.
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.