Rats intraperitoneally administered 5-thio- D-glucopyranose rapidly develop glucosuria and hyperglycemia. With a dose of 50 mg/kg the blood D-glucose rises to approximately 300 mg/100 ml within 2.5 hr, then drops to 160 mg/100 ml within 6 hr. Rats given booster doses of 5-thio-D-glucopyranose every hour maintain blood D-glucose levels of 300 mg/100 ml. The same effect is observed in rats with ligated kidneys given a single 50-mg/kg dose of 5-thio-D-glucopyranose. Administration of insulin completely nullifies the diabetogenic effect. Livers of rats fasted for 20 hr had 50% less glycogen 2.5 hr after injection of 50 mg/kg of 5-thio-D-glucopyranose than saline-injected controls. Rats injected with 5-thio-D-glucopyranose excreted 97% of the sugar in the urine indicating little or no metabolism of 5-thio-D-glucopyranose. Investigations with rat liver slices, kidney slices, and diaphragms show a marked decrease in the uptake of D-glucose by these tissues when molarity ratios of 5-thio-D-glucopyranose/D-glucose from 0.5 to 1 are present in the initial incubation media at 37°. 5-Thio- D-glucopyranose did not inhibit the metabolism of d- glucose in kidney homogenates but did slightly inhibit glycolysis (8.3% with a molarity ratio 5-thio-D-glucopyranose/D-glucose of 0.50). After a series of three injections of 5-thio-D-glucopyranose at 2-hr intervals there is a 43% increase in the total catechol amine content of the urine. A 73% increase in blood nonesterified fatty acids of rats fasted for 16 hr is observed 0.5 hr af er a single 150-mg/kg dose of 5-thio-D-glucopyranose. The nonesterified fatty acid level then returns to a normal fasting level within 2 hr. 5- Thio-D-glucopyranose is neither a substrate nor an inhibitor of D-glucose oxidase which is used to analyze for D-glucose. 5-Thio-D-glucopyranose does not inhibit yeast hexokinase but acts as a poor substate. Kinetic measurements give a Km of 4 × 10−3 M and a Vmax (glucose — 100) of 1.3. © 1968, American Chemical Society. All rights reserved.
