Interference of D-mannoheptulose with D-glucose phosphorylation, metabolism and functional effects: comparison between liver, parotid cells and pancreatic islets.
D-mannoheptulose is currently used as a tool to inhibit, in a competitive manner, D-glucose phosphorylation, metabolism and functional effects in the pancreatic islet B-cell. In order to better understand the mode of action of the heptose, we have explored its effect upon D-glucose phosphorylation in liver, parotid cells and islet homogenates, this allowing to characterize the interference of the heptose with glucokinase and/or hexokinase. The effect of D-mannoheptulose upon the metabolism of D-glucose was also examined in both intact parotid cells and pancreatic islets. Last, the effect of D-mannoheptulose upon glucose-stimulated insulin release was reinvestigated over large concentration ranges of both the heptose and hexose. The experimental data revealed a mixed type of D-mannoheptulose inhibitory action upon D-glucose phosphorylation, predominantly of the non-competitive and competitive type, in liver and parotid homogenates, respectively. Despite efficient inhibition of hexose phosphorylation in both parotid cell and islet homogenates, the heptose suppressed the metabolic and functional responses to D-glucose only in pancreatic islets, whilst failing to affect adversely D-glucose catabolism in parotid cells. These findings suggest that factors such as the intracellular transport and availability of the heptose may interfere with the expression of its antagonistic action upon D-glucose metabolism.
Scruel
O
O
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Vanhoutte
C
C
Sener
A
A
Malaisse
W J
WJ
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006593:Hexokinase / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology; D007651:Keto Acids / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008356:Mannoheptulose / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010306:Parotid Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D007527:Isoenzymes; D007651:Keto Acids; D008356:Mannoheptulose; C013082:alpha-ketoisocaproic acid; D006593:Hexokinase; D005947:Glucose