The effect of insulin and hydrocortisone on the in vivo tissue uptake of 2-deoxyglucose in mice.
The purpose of this study was to assess the feasibility and limitations of using the uptake of 14C-2-deoxyglucose (14C-2DG) under nonsteady-state conditions in the conscious mouse as a screening model for detecting changes in glucose uptake. Male, Swiss--Webster mice were administered an i.v. dose of 2-deoxyglucose (2DG, 50-75 mg/kg) with 14C-2DG (20 microCi/kg, 44-66 microCi/mmole). The levels of 14C-2DG were measured in gastrocnemius muscle, retroperitoneal fat, liver, cerebral cortex, and blood. Insulin (2 U/kg) s.c. significantly reduced 2DG levels in blood and liver compared to saline controls but significantly increased 2DG levels in muscle and fat. There was no effect on cerebral cortex 2DG uptake. Hydrocortisone (HC) treatment (300 mg/kg, i.p.) significantly reduced brain and muscle 2DG uptake. The effect of HC on brain 2DG levels may be caused by an indirect effect since determination of the 14C-sorbitol space indicated that HC reduced sorbitol levels in the brain when compared to saline controls, a reduction not detected in muscle. The limitations of the model seem to involve the brain and liver. Increasing glucose concentrations (i.v. glucose challenge) lead to decreased 2DG brain levels. It also appears that 2DG may not be reflecting glucose assimilation in the liver. However, it appears that the in vivo 2DG uptake model is a useful screening method for detecting changes in 2DG assimilation in fat and muscle following drug treatment.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000097:blood / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D013012:Sorbitol / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects
D001786:Blood Glucose; D003837:Deoxy Sugars; D005958:Glucosephosphates; D007328:Insulin; C015785:2-deoxyglucose-6-phosphate; D013012:Sorbitol; D019298:Glucose-6-Phosphate; D003847:Deoxyglucose; D006854:Hydrocortisone