Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1
| Autor: | B Weiss, J Yao, Maria Gutierrez, R N K Snyder, Deborah Hilliard, Patrick Larson, Elizabeth Migoya, Nancy A. Thornberry, Jens J. Holst, Ranabir SinhaRoy, K A Pryor, John M. Amatruda, Michael Tanen, Lan Zhu, Gary A. Herman, Raynald Bergeron, D. E. Williams-Herman, John A. Wagner, Fang Liu, Guoqiang Jiang, Carolyn F. Deacon, Jutta Miller |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Adolescent Incretin Glucagon Mice Young Adult Pharmacokinetics Double-Blind Method In vivo Glucagon-Like Peptide 1 Internal medicine medicine Animals Humans Pharmacology (medical) Obesity Dipeptidyl peptidase-4 Pharmacology chemistry.chemical_classification Dipeptidyl-Peptidase IV Inhibitors Cross-Over Studies Chemistry digestive oral and skin physiology nutritional and metabolic diseases Middle Aged Glucagon-like peptide-1 Metformin Mice Inbred C57BL Endocrinology Enzyme Drug Therapy Combination Female hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 88(6) |
| ISSN: | 1532-6535 |
| Popis: | The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma. |
| Databáze: | OpenAIRE |
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