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Action of 5-thio-D-glucose on D-glucose metabolism: possible mechanism for diabetogenic effect

MJ Kelley and TS Chen

The effect of 5-thio-D-glucose (5-TG) on the hexosemonophosphate shunt (HMS) and on aerobic glycolysis was studied in the mouse small intestine. A time- and dose-dependent inhibition of 14CO2 production from D-[1-14C] or D-[6-14C]glucose was observed by 5-TG in vitro. Using everted rings of intestine, the HMS (measured by the C-1/C-6 ratio of 14CO2 produced) was inhibited approximately 60% relative to control by 11.0 mM 5-TG. The 14CO2 produced from D-[6-14C]glucose was not inhibited markedly until incubations were lengthened to 45 min or longer. The HMS in everted rings from mice treated with 5-TG at 50 mg/kg or 1.5 g/kg i.p. increased 200 or 130%, respectively, compared to saline-treated controls. In contrast, 14CO2 produced from D-[6- 14C]glucose was inhibited at both doses. Plasma D-glucose levels were measured 2 hr after treatment and were increased 100% at the low dose or 360% at the high dose, relative to controls (84.1 +/- 3.8 mg/100 ml). This study demonstrated that 5-TG inhibits D-glucose utilization in the mouse small intestine, which may contribute to the diabetogenic effect observed in vivo.

Volume 232, Issue 3, pp. 760-763, 03/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1985 by the American Society for Pharmacology and Experimental Therapeutics.