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

  • Zakariassen HL Section of Experimental Animal Models, Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
  • John LM Obesity Pharmacology, Novo Nordisk A/S, Måløv, Denmark.
  • Lutz TA Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
  • 2020-05-05
Published in:
  • Basic & clinical pharmacology & toxicology. - 2020
amylin
amylin receptor agonists
calcitonin receptor agonists
energy balance
metabolic disease
salmon calcitonin
English The 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 with obesity. Treatment with amylin and calcitonin receptor agonists reduces food intake and induces weight loss in several animal models, and a number of companies have started clinical testing for peptide analogues in the treatment of obesity and/or type 2 diabetes. Studies predominantly performed in rodent models show that amylin and the dual amylin/calcitonin receptor agonist salmon calcitonin achieve their metabolic effects by engaging areas in the brain associated with regulating homeostatic energy balance. In particular, signalling via neuronal circuits in the caudal hindbrain and the hypothalamus is implicated in mediating effects on food intake and energy expenditure. We review the current literature investigating the interaction of amylin/calcitonin receptor agonists with neurocircuits that induce the observed metabolic effects. Moreover, the status of drug development of amylin and calcitonin receptor agonists for the treatment of metabolic diseases is summarized.
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  • English
Open access status
bronze
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https://sonar.ch/global/documents/151569
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