Contrasting modes of action of D-glucose and 3-O-methyl-D-glucose as protectors of the rat pancreatic B-cell against alloxan.
Both D-glucose and its nonmetabolized analog 3-O-methyl-D-glucose are known to protect the pancreatic B-cell against the toxic action of alloxan, as if the protective action of hexoses were to involve a membrane-associated glucoreceptor site. In the present study, the protective actions of the two hexoses were found to differ from one another in several respects. Using the process of glucose-stimulated insulin release by rat pancreatic islets as an index of alloxan cytotoxicity, we observed that the protective action of D-glucose was suppressed by D-mannoheptulose and menadione, impaired by NH4Cl, and little affected by aminooxyacetate. These findings and the fact that D-glucose failed to decrease [2-14C]alloxan uptake by the islets suggest that the protective action of D-glucose depends on an increase in the generation rate of reducing equivalents (NADH and NADPH). The latter view is supported by the observation that the protective action of a noncarbohydrate nutrient, 2-ketoisocaproate, was also abolished by menadione. Incidentally, the protective action of 2-ketoisocaproate was apparently a mitochondrial phenomenon, it not being suppressed by aminooxyacetate. In contrast to that of glucose, the protective action of 3-O-methyl-D-glucose was unaffected by D-mannoheptulose, failed to be totally suppressed by menadione, and coincided with a decreased uptake of [2-14C]-alloxan by the islets. It is concluded that the protective action of D-glucose in linked to the metabolism of the sugar in islet cells, whereas that of 3-O-methyl-D-glucose results from inhibition of alloxan uptake. This conclusion reinforces our opinion that the presence in the B-cell of an alleged stereospecific membrane glucoreceptor represents a mythical concept.
D019325:3-O-Methylglucose; D000496:Alloxan / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007651:Keto Acids / Q000494:pharmacology; D008356:Mannoheptulose / Q000494:pharmacology; D008757:Methylglucosides / Q000494:pharmacology*; D008759:Methylglycosides / Q000494:pharmacology*; D051381:Rats; D014812:Vitamin K / Q000494:pharmacology
D007328:Insulin; D007651:Keto Acids; D008757:Methylglucosides; D008759:Methylglycosides; D014812:Vitamin K; D019325:3-O-Methylglucose; D000625:Aminooxyacetic Acid; D008356:Mannoheptulose; D000496:Alloxan; C013082:alpha-ketoisocaproic acid; D005947:Glucose