Action of 5-thio-D-glucose on D-glucose metabolism: possible mechanism for diabetogenic effect.
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.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010427:Pentose Phosphate Pathway / Q000187:drug effects
D001786:Blood Glucose; D002245:Carbon Dioxide; C003002:5-thio-D-glucose; D005947:Glucose