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      Central Control of Feeding Behavior by the Secretin, PACAP, and Glucagon Family of Peptides

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          Abstract

          Constituting a group of structurally related brain-gut peptides, secretin (SCT), pituitary adenylate cyclase-activating peptide (PACAP), and glucagon (GCG) family of peptide hormones exert their functions via interactions with the class B1 G protein-coupled receptors. In recent years, the roles of these peptides in neuroendocrine control of feeding behavior have been a specific area of research focus for development of potential therapeutic drug targets to combat obesity and metabolic disorders. As a result, some members in the family and their analogs have already been utilized as therapeutic agents in clinical application. This review aims to provide an overview of the current understanding on the important role of SCT, PACAP, and GCG family of peptides in central control of feeding behavior.

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          Most cited references176

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          GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.

          In healthy humans, the incretin glucagon-like peptide 1 (GLP-1) is secreted after eating and lowers glucose concentrations by augmenting insulin secretion and suppressing glucagon release. Additional effects of GLP-1 include retardation of gastric emptying, suppression of appetite and, potentially, inhibition of β-cell apoptosis. Native GLP-1 is degraded within ~2-3 min in the circulation; various GLP-1 receptor agonists have, therefore, been developed to provide prolonged in vivo actions. These GLP-1 receptor agonists can be categorized as either short-acting compounds, which provide short-lived receptor activation (such as exenatide and lixisenatide) or as long-acting compounds (for example albiglutide, dulaglutide, exenatide long-acting release, and liraglutide), which activate the GLP-1 receptor continuously at their recommended dose. The pharmacokinetic differences between these drugs lead to important differences in their pharmacodynamic profiles. The short-acting GLP-1 receptor agonists primarily lower postprandial blood glucose levels through inhibition of gastric emptying, whereas the long-acting compounds have a stronger effect on fasting glucose levels, which is mediated predominantly through their insulinotropic and glucagonostatic actions. The adverse effect profiles of these compounds also differ. The individual properties of the various GLP-1 receptor agonists might enable incretin-based treatment of type 2 diabetes mellitus to be tailored to the needs of each patient.
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            The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

            We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
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              Anatomy and regulation of the central melanocortin system.

              Roger Cone (2005)
              The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                07 February 2017
                2017
                : 8
                : 18
                Affiliations
                [1] 1School of Biological Sciences, The University of Hong Kong , Hong Kong, China
                Author notes

                Edited by: Hubert Vaudry, University of Rouen, France

                Reviewed by: Lourdes Mounien, Aix-Marseille University, France; SuJean Choi, Marquette University, USA

                *Correspondence: Billy Kwok Chong Chow, bkcc@ 123456hku.hk

                Specialty section: This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2017.00018
                5293785
                28144230
                124a529f-e8bc-44ec-95f1-e6b3f3ad895b
                Copyright © 2017 Sekar, Wang and Chow.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 November 2016
                : 18 January 2017
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 216, Pages: 14, Words: 13336
                Funding
                Funded by: Research Grants Council, University Grants Committee 10.13039/501100002920
                Award ID: GRF 17105514, HKU6/CRF/11G
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                secretin,pacap,and glucagon family peptides,hypothalamus,feeding behavior,energy homeostasis,metabolic diseases

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