Hypoglycaemic and hypoketonaemic effects of single and repeated oral doses of methyl palmoxirate (methyl 2-tetradecylglycidate) in streptozotocin/alloxan-induced diabetic dogs.
1. The hypoglycaemic and hypoketonaemic effects of orally administered methyl palmoxirate were studied in streptozotocin/alloxan-induced diabetic dogs. 2. Single oral 50 mg doses (approximately 7.5 mg kg-1) of methyl palmoxirate produced statistically significant reductions of plasma glucose (32 +/- 6% maximum reduction from baseline) and ketones (74 +/- 12% maximum reduction from baseline), with the peak effect on plasma ketones (3.5 h) preceding that for plasma glucose (6.0 h). 3. Lower doses (0.7-2.0 mg kg-1 daily) of methyl palmoxirate given repeatedly for seven days produced reductions of blood glucose and ketones equivalent to those produced with the higher single dose. Maximal reductions of plasma ketones were generally observed following the first dose of drug, whereas significant lowering of plasma glucose required several days of continuous dosing. 4. Repeated daily doses of methyl palmoxirate markedly reduced the overnight fasting ketone levels but not glucose levels of diabetic dogs. 5. In conclusion, administration of the fatty acid oxidation inhibitor methyl palmoxirate, in the absence of concomitant insulin therapy, was able to lower the plasma glucose and ketone levels of insulin-deficient streptozotocin/alloxan diabetic dogs. Only the plasma ketones were decreased to normal by this treatment.
Tuman
R W
RW
Department of Biological Research, McNeil Pharmaceutical, Pennsylvania 19477.
Tutwiler
G F
GF
Joseph
J M
JM
Wallace
N H
NH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004285:Dogs; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000097:blood; D007004:Hypoglycemic Agents; D007651:Keto Acids / Q000097:blood*; D011422:Propionates / Q000494:pharmacology*
D001786:Blood Glucose; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D006885:Hydroxybutyrates; D007004:Hypoglycemic Agents; D007651:Keto Acids; D011422:Propionates; C017522:methyl 2-tetradecylglycidate