Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
| Autor: | Leif K. Larsen, Henrik H. Hansen, Jacob Jelsing, Harald Tammen, Niels Vrang, Peter W. Haebel, Rikke V. Grônlund, Thomas Klein, Tamara Baader-Pagler |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist Male medicine.medical_specialty Combination therapy medicine.drug_class Science Mice Obese 030209 endocrinology & metabolism Linagliptin Dipeptidyl peptidase Article 03 medical and health sciences Mice 0302 clinical medicine Weight loss Internal medicine medicine Animals Pharmacology Dipeptidyl-Peptidase IV Inhibitors Multidisciplinary Chemistry digestive oral and skin physiology Endocrine system and metabolic diseases Receptors Neuropeptide Y 030104 developmental biology Endocrinology Anorectic Medicine medicine.symptom Diet-induced obese Homeostasis medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Dipeptidyl peptidase IV (DPP-IV) inhibitors improve glycemic control by prolonging the action of glucagon-like peptide-1 (GLP-1). In contrast to GLP-1 analogues, DPP-IV inhibitors are weight-neutral. DPP-IV cleavage of PYY and NPY gives rise to PYY3-36 and NPY3-36 which exert potent anorectic action by stimulating Y2 receptor (Y2R) function. This invites the possibility that DPP-IV inhibitors could be weight-neutral by preventing conversion of PYY/NPY to Y2R-selective peptide agonists. We therefore investigated whether co-administration of an Y2R-selective agonist could unmask potential weight lowering effects of the DDP-IV inhibitor linagliptin. Male diet-induced obese (DIO) mice received once daily subcutaneous treatment with linagliptin (3 mg/kg), a Y2R-selective PYY3-36 analogue (3 or 30 nmol/kg) or combination therapy for 14 days. While linagliptin promoted marginal weight loss without influencing food intake, the PYY3-36 analogue induced significant weight loss and transient suppression of food intake. Both compounds significantly improved oral glucose tolerance. Because combination treatment did not further improve weight loss and glucose tolerance in DIO mice, this suggests that potential negative modulatory effects of DPP-IV inhibitors on endogenous Y2R peptide agonist activity is likely insufficient to influence weight homeostasis. Weight-neutrality of DPP-IV inhibitors may therefore not be explained by counter-regulatory effects on PYY/NPY responses. |
| Databáze: | OpenAIRE |
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