Ceftezole, a cephem antibiotic, is an alpha-glucosidase inhibitor with in vivo anti-diabetic activity.
Using a high throughput-compatible assay to screen for potential alpha-glucosidase inhibitors, we found that the beta-lactam antibiotic ceftezole exhibited potent alpha-glucosidase inhibitory activity. In in vitro alpha-glucosidase assays, ceftezole was shown to be a reversible, non-competitive inhibitor of yeast alpha-glucosidase with a Ki value of 5.78 x 10(-7) M when the enzyme mixture was pretreated with ceftezole. Using an in vivo streptozotocin-induced mouse model, we confirmed that blood glucose levels decreased by 30% 20 min after ceftezole treatment (10 mg/kg/day). Expression levels of glycogen synthase kinase-3, peroxisome proliferator-activated receptor-gamma, and uncoupling protein-3 mRNA were also slightly decreased compared to controls following ceftezole treatment. Taken together, these in vivo and in vitro results suggest that ceftezole may be a clinically useful anti-diabetic compound.
Lee
Dong-Sun
DS
Department of Microbiology, Kyungpook National University, Daegu 702-701, Korea.
Lee
Jin-Man
JM
Kim
Sung-Uk
SU
Chang
Kyu-Tae
KT
Lee
Sang-Han
SH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D015281:Cefmenoxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D017931:DNA Primers; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; C049493:cefteram; D038362:Glycogen Synthase Kinase 3; D015281:Cefmenoxime