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

Abstract

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, inhibiting86Rb outflow, and augmenting45Ca 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, 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.

Insulinotropic action of β-l-glucose pentaacetate

“…The pentaacetate ester of ␤-Lglucose (1.7 mM), however, inhibited (P Ͻ 0.02 or less) the tritiation of islet peptides in islets exposed to either 4.2 mM D-glucose or 10.0 mM L-leucine. This contrasts with the fact that the insulinotropic action of ␤-Lglucose pentaacetate is more marked in the presence of D-glucose or L-leucine than in the absence of exogenous nutrient (21).…”

“…Secretory data. The insulinotropic action of ␤-Lglucose pentaacetate was previously explored in islets incubated either in the absence of any exogenous nutrient (21) or in the presence of 8.3 mM D-glucose, 10.0 mM L-leucine (21), or 10.0 mM succinic acid dimethyl ester (18). In the absence of another exogenous nutrient or at a noninsulinotropic concentration of D-glucose (4.0 mM), the increase in insulin output caused by ␤-L-glucose pentaacetate is quite modest and, on occasion, fails to achieve statistical significance.…”

“…pancreatic islets; insulin release THE POLYACETATE ESTERS of several monosaccharides were recently proposed as tools to increase the metabolic efficiency of the corresponding carbohydrates. For instance, ␣-D-glucose pentaacetate was found to be metabolized and to stimulate insulin release at higher rates than unesterified D-glucose in rat pancreatic islets (21,31). Likewise, D-mannoheptulose hexaacetate was reported to inhibit D-glucose metabolism in parotid cells and erythrocytes, which are otherwise resistant to the unesterified heptose (11,19).…”

“…In experiments dealing with the mode of action of ␣-D-glucose pentaacetate in pancreatic islet cells, the pentaacetate ester of ␤-L-glucose was unexpectedly found also to stimulate insulin release, albeit to a lesser extent than ␣-D-glucose pentaacetate (21). The insulinreleasing capacity of ␤-L-glucose pentaacetate does not seem to be attributable to the catabolism of its acetate moiety, since ␤-D-galactose pentaacetate, which is as efficiently taken up and hydrolyzed in isolated islets as ␣-D-glucose pentaacetate (34), fails to display any positive effect on insulin secretion (21).…”

Monosaccharide Esters : Clinically Relevant ?

“…In islets from spontaneously diabetic Goto rats, the glucose ester enhances to a greater relative extent the secretory response to L-leucine, as compared to islets from control rats (8). Last, at variance with the hypoglycaemic sulfonylureas and meglitinide analogs currently used as antidiabetic agents, glucose pentaacetate stimulates biosynthetic activity in isolated rat pancreatic islets (9,10). Interestingly, the ester was also found to stimulate both insulin synthesis and release in pancreatic islets from human subjects (11).…”