Insulinotropic action of the polyacetate esters of metabolized and non-metabolized monosaccharides in pancreatic islets from normal and diabetic rats.
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 1.7 mM concentration. L-Leucine-stimulated insulin release was also increased by alpha-D-glucose pentaacetate, but not significantly affected by beta-D-galactose pentaacetate, beta-L-glucose pentaacetate, 2-deoxy-D-glucose tetraacetate and D-mannoheptulose hexaacetate in the islets of diabetic animals. These findings suggest a dual mode of action of the esters in the pancreatic islet B-cell, involving both the metabolic response to their sugar moieties and a direct effect of the esters themselves upon a specific receptor system. It is proposed that selected esters could be used as insulinotropic tools in non-insulin-dependent diabetes mellitus.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Laghmich
A
A
Ladrière
L
L
Kadiata
M M
MM
Sener
A
A
D000085:Acetates / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008297:Male; D009005:Monosaccharides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D000085:Acetates; D007328:Insulin; D009005:Monosaccharides; D007930:Leucine; D005947:Glucose