Insulinotropic action of alpha-D-glucose pentaacetate: metabolic aspects.
The metabolism and metabolic effects of alpha-D-glucose pentaacetate were investigated in isolated rat pancreatic islets. Several findings were compatible with the view that the insulinotropic action of alpha-D-glucose pentaacetate is causally related to its capacity to act as a fuel in the islet B-cell. First, the ester was efficiently taken up and hydrolyzed with resulting accumulation of D-glucose in the islet cells. Second, the conversion of alpha-D-[5-3H]glucose pentaacetate to 3HOH and that of alpha-D-[U-14C]glucose pentaacetate to 14CO2 exceeded those found at an equimolar concentration (1.7 mM) of D-glucose and were both inhibited by 2-deoxy-D-glucose (16.7 mM). Last, the ester inhibited the catabolism of both exogenous D-glucose or endogenous fatty acids. Yet, an apparent dissociation between the metabolic and secretory responses to the ester was suggested by the failure of alpha-D-glucose pentaacetate to increase O2 uptake by the islets. Moreover, there were striking differences between the catabolism of the ester and that of unesterified D-glucose, such as a much higher intracellular D-glucose content and an insensitiveness to the inhibitory action of D-mannoheptulose in islets exposed to alpha-D-glucose pentaacetate. Likewise, the ratio between hexose oxidation and utilization was lower for alpha-D-glucose pentaacetate than for unesterified D-glucose in islets concomitantly exposed to the hexose and its ester. It is proposed, therefore, that the insulinotropic action of alpha-D-glucose pentaacetate, although probably linked to the intracellular generation of D-glucose from the ester, may not involve the same coupling process between metabolic and functional events as that currently implied in the process of glucose-stimulated insulin release.
Sener
A
A
Laboratory of Experimental Medicine, Brussels Free University, Brussels, B-1070, Belgium.
Welsh
N
N
Malaisse-Lagae
F
F
Kadiata
M M
MM
Malaisse
W J
WJ
D000085:Acetates / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008356:Mannoheptulose / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D000085:Acetates; D000963:Antimetabolites; D002250:Carbon Radioisotopes; D007328:Insulin; C105128:glucose pentaacetate; D008356:Mannoheptulose; D003847:Deoxyglucose; D005947:Glucose