Comparison of efficacies of a dipeptidyl peptidase IV inhibitor and alpha-glucosidase inhibitors in oral carbohydrate and meal tolerance tests and the effects of their combination in mice.

Abstract

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia.

• Authors: Kazuto Yamazaki, Takashi Inoue, Nobuyuki Yasuda, Yoshiaki Sato, Tadashi Nagakura, Osamu Takenaka, Richard Clark, Takao Saeki, Isao Tanaka
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 104 Issue 1 Pg. 29-38 (May 2007) ISSN: 1347-8613 [Print] Japan
• PMID: 17485917 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo(4,5-d)pyridazin-4-one tosylate
• Blood Glucose
• Dietary Sucrose
• Dipeptidyl-Peptidase IV Inhibitors
• Enzyme Inhibitors
• Glycoside Hydrolase Inhibitors
• Hypoglycemic Agents
• Imidazoles
• Insulin
• Pyridazines
• Tosyl Compounds
• Ensure formulated food
• Inositol
• Glucagon-Like Peptide 1
• voglibose
• Acarbose

Topics

• Acarbose (administration & dosage, pharmacokinetics, therapeutic use)
• Administration, Oral
• Animals
• Area Under Curve
• Blood Glucose (metabolism)
• Carbohydrate Metabolism (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy)
• Dietary Sucrose (administration & dosage, metabolism)
• Dipeptidyl-Peptidase IV Inhibitors
• Drug Therapy, Combination
• Enzyme Inhibitors (administration & dosage, pharmacokinetics, therapeutic use)
• Food, Formulated
• Glucagon-Like Peptide 1 (blood)
• Glucose Tolerance Test (methods)
• Glycoside Hydrolase Inhibitors
• Hyperglycemia (blood, prevention & control)
• Hypoglycemic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Imidazoles (administration & dosage, pharmacokinetics, therapeutic use)
• Injections, Intravenous
• Inositol (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
• Insulin (blood)
• Male
• Mice
• Mice, Inbred C57BL
• Postprandial Period
• Pyridazines (administration & dosage, pharmacokinetics, therapeutic use)
• Tosyl Compounds (administration & dosage, pharmacokinetics, therapeutic use)