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Central control of energy balance by amylin and calcitonin receptor agonists and their potential for treatment of metabolic diseases [PDF]

Basic and Clinical Pharmacology and Toxicology, 2020
AbstractThe prevalence of obesity and associated comorbidities such as type 2 diabetes and cardiovascular disease is increasing globally. Body‐weight loss reduces the risk of morbidity and mortality in obese individuals, and thus, pharmacotherapies that induce weight loss can be of great value in improving the health and well‐being of people living ...
Hannah Louise Zakariassen, Thomas Alexander Lutz   +1 more
exaly   +6 more sources

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Oral delivery of the amylin receptor agonist pramlintide

Peptide Science, 2023
Abstract Amylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico‐chemical compatibility when co‐formulated with insulin. Here, we report the design and characterization
Celimar Sinézia, Tháyna Sisnande, Luis Peña Icart, Luís Maurício T. R. Lima   +3 more
openaire   +1 more source

Design, synthesis and preclinical evaluation of bio-conjugated amylinomimetic peptides as long-acting amylin receptor agonists

European Journal of Medicinal Chemistry, 2022
Pramlintide is an equipotent amylin analogue that reduces food intake and body weight in obese subjects and has been clinically approved as an adjunctive therapy for the treatment of adult diabetic patients. However, due to its extremely short half-life in vivo, a regimen of multiple daily administrations is required for achieving clinical ...
Wenying Jian, Raymond Patch
exaly   +3 more sources

Amylin is an agonist of the renal porcine calcitonin receptor.

Endocrinology, 1994
The cloned renal porcine calcitonin (pCT) receptor cDNA expressed by transient transfection in COS-1 cells or stable transfection in HEK-293 cells was assayed for interaction with CT, amylin, and CT gene-related peptide. Both [125I]salmon CT ([125I]sCT) and [125I]rat amylin displayed specific binding to transfected cells, and in both cases, pCT and rat
P M, Sexton, S, Houssami, C L, Brady, D E, Myers, D M, Findlay   +4 more
openaire   +3 more sources

Improved metabolic efficacy of a dual amylin and calcitonin receptor agonist when combined with semaglutide or empagliflozin

European Journal of Pharmacology, 2023
Pharmacotherapies for obesity and type 2 diabetes (T2D) are thought to bridge the gap between lifestyle modification and the weight loss obtained with bariatric surgery. Although the effect of monotherapies, namely amylin and glucagon-like peptide-1 receptor (GLP-1R) agonists, has shown great potential, combination therapy is now becoming a strategy to
Simone A. Melander, Anna Katri, Morten A. Karsdal, Kim Henriksen   +3 more
openaire   +2 more sources

Does receptor balance matter? – Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models

Biomedicine and Pharmacotherapy, 2022
Cagrilintide is a novel long-acting amylin receptor agonist, which has shown a potent induction of weight loss. Interestingly, cagrilintide is a Dual Amylin and Calcitonin Receptor Agonist (DACRA) derived from an amylin backbone. Another class of long-acting DACRAs exists, namely the KBPs.
A T, Larsen, K E, Mohamed, N, Sonne, E, Bredtoft, F, Andersen, M A, Karsdal, K, Henriksen   +6 more
exaly   +3 more sources

Amylin receptor agonists: a novel pharmacological approach in the management of insulin-treated diabetes mellitus

Expert Opinion on Investigational Drugs, 2001
Amylin is a peptide hormone which is co-secreted with insulin from the pancreatic beta-cell. Type 1 diabetic individuals and some Type 2 diabetic individuals are characterised by amylin deficiency. Animal experiments have revealed several actions of amylin on intermediary metabolism, of these some have been demonstrated to be of potential physiological
Schmitz, O., Brock, B., Ørskov, L., Nyholm, B.   +3 more
openaire   +3 more sources

The long-acting amylin/calcitonin receptor agonist ZP5461 suppresses food intake and body weight in male rats

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2021
The peptide hormone amylin reduces food intake and body weight and is an attractive candidate target for novel pharmacotherapies to treat obesity. However, the short half-life of native amylin and amylin analogs like pramlintide limits these compounds’ potential utility in promoting sustained negative energy balance.
Lauren M. Stein, Lauren E. McGrath, Rinzin Lhamo, Kieran Koch-Laskowski, Samantha M. Fortin, Jolanta Skarbaliene, Tamara Baader-Pagler, Rasmus Just, Matthew R. Hayes, Elizabeth G. Mietlicki-Baase   +9 more
openaire   +2 more sources

Treatment sequencing using the dual amylin and calcitonin receptor agonist KBP-336 and semaglutide results in durable weight loss

European Journal of Pharmacology, 2023
Long-acting dual amylin and calcitonin receptor agonists (DACRAs) hold great promise as potential treatments for obesity and its associated comorbidities. These agents have demonstrated beneficial effects on body weight, glucose control, and insulin action mirroring the effects observed with glucagon-like peptide-1 (GLP-1) agonist treatment. Strategies
Anna Thorsø Larsen, Morten A. Karsdal, Kim Henriksen   +2 more
openaire   +2 more sources

Structure, Self-Association, and Aggregation Properties of a Long-Acting Amylin Receptor Agonist

Molecular Pharmaceutics
Pharmacokinetic (PK) properties of therapeutic peptides can be extended through covalent conjugation to albumin-binding fatty acids. The present study examines the effects of fatty acid conjugation and vehicle composition on structure, self-association pattern, and aggregation propensity of an amylin analogue.
Christian Poulsen, Mathias Norrman, Jens Kaalby Thomsen, Per-Olof Wahlund   +3 more
openaire   +2 more sources