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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Treatment of diabetes and obesity by rationally designed peptide agonists functioning at multiple metabolic receptors.
In: (10th ESPE Advanced Seminar in Developmental Endocrinology, 10 June 2016, Ulm). Karger, 2017. 165-182 (Endocr. Dev. ; 32)
Obesity and its comorbidities such as type 2 diabetes constitute major worldwide health threats, and the identification of an effective medical intervention has emerged as a global priority. The limited effectiveness of historical, anti-obesity treatments is commonly attributed to the complexity of the disease and the redundancy of metabolic regulatory mechanisms that sustain body weight. At the forefront of obesity research is the development of combinational drug therapies that simultaneously target multiple regulatory pathways, which promote dysfunctional metabolism. Recently, molecularly crafted unimolecular "multi-agonism" of balanced activity at 3 key receptors involved in metabolism and specifically the glucagon-like peptide (GLP)-1 receptor, glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon receptor was reported as superior to conventional monoagonist therapy. These mixed peptide agonists are designed to pharmacologically integrate the insulinotropic and anorexigenic effects of GLP-1, the thermogenic and lipolytic activities of glucagon, and the insulinotropic and insulin sensitizing properties of GIP. The molecular mechanism of these purposefully promiscuous ligands is not completely understood, however, recent studies in pancreatic beta cells point to the prospect of a complex signaling network that can magnify the signaling of multi-agonist ligands. The activation of this signalosome might explain the additional therapeutic benefit inherent to simultaneous cellular activation through multiple metabolic receptors.
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Publikationstyp
Artikel: Konferenzbeitrag
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
1421-7082
e-ISSN
1662-2979
Konferenztitel
10th ESPE Advanced Seminar in Developmental Endocrinology
Konferzenzdatum
10 June 2016
Konferenzort
Ulm
Zeitschrift
Endocrine Development
Quellenangaben
Band: 32,
Seiten: 165-182
Verlag
Karger
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Diabetes and Obesity (IDO)