Insulinotropic action of alpha-D-glucose pentaacetate: functional aspects.
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.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Sánchez-Soto
C
C
Larrieta
M E
ME
Hiriart
M
M
Jijakli
H
H
Viñambres
C
C
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Kirk
O
O
Kadiata
M M
MM
Sener
A
A
D019325:3-O-Methylglucose / Q000494:pharmacology; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013806:Theophylline / Q000494:pharmacology
D007328:Insulin; D019325:3-O-Methylglucose; C105128:glucose pentaacetate; D003571:Cytochalasin B; D004533:Egtazic Acid; D013806:Theophylline; D007930:Leucine; D005947:Glucose; D002122:Calcium Chloride