Adrenomedullin and glucagon-like peptide-1 have additive effects on food intake in mice

Abstract

Adrenomedullin (ADM) is a vasoactive peptide expressed in several peripheral organs and known primarily for its beneficial vasoactive effects. However, ADM is also known to inhibit insulin secretion, and central administration of ADM has been shown to elicit anorexigenic effects. Here, we investigated if peripheral co-administration of ADM and glucagon-like peptide 1 (GLP-1) could subdue the hypoglycaemic effects of ADM while enhancing its anorectic properties. The effects of mono- and combination therapy of ADM and GLP-1 on appetite regulation and glucose homeostasis were assessed acutely in male NMRI mice for 12 h, while effects on glucose homeostasis were assessed by oral glucose tolerance tests (OGTT). While the monotherapy with GLP-1 and ADM resulted in modest anorexigenic effects, co-administration of the two peptides led to a marked additive reduction in food intake. Moreover, while OGTT-evoked blood glucose-excursions were significantly increased by ADM monotherapy, co-administration of ADM with a lower dose of GLP-1 normalized glucose excursions. In conclusion, we demonstrate additive anorectic effects of ADM and GLP-1, and that GLP-1 co-administration prevents ADM-induced impairment of glucose tolerance, suggesting that ADM could be potential anti-obesity target when combined with GLP-1 agonist therapy.

Keywords: ADM; Adrenomedullin; Diabetes; Food intake; GLP-1; Glucagon-like peptide 1; Glucose tolerance; Insulin secretion; Obesity.