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Major contributions of comparative endocrinology to the development and exploitation of the incretin concept

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Conlon, J. Michael, Patterson, Steven and Flatt, Peter (2006) Major contributions of comparative endocrinology to the development and exploitation of the incretin concept. JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-COMPARATIVE EXPERIMENTAL BIOLOGY, 305A (9). pp. 781-786. [Journal article]

Full text not available from this repository.

DOI: 10.1002/jez.a.312

Abstract

An incretin is a factor released by the gut in response to nutrients that facilitates uptake of glucose by peripheral tissues. The incretin concept predates the discovery of insulin but it is now clear that incretins act by stimulating secretion of this hormone. As glucagon has insulin-releasing activity, it was speculated that intestinal glucagon-like immunoreactivity (enteroglucagon) was involved in the incretin effect but it was an achievement in the field of comparative endocrinology that led to the demonstration that the preproglucagon gene encodes the most potent incretin in the human. Characterization of cloned cDNAs encoding two preproglucagons from the Brockmann body of the anglerfish Lophius americanus demonstrated that the glucagon sequence is flanked by a 34 amino-acid-residue sequence with appreciable structural similarity to glucagon that was termed glucagon-like peptide (GLP). A 36 amino-acid-residue ortholog of anglerfish GLP was subsequently identified in human preproglucagon but this peptide had only weak insulin-releasing activity. However, alignment of GLP sequences from human and teleost fish showed that the human ortholog is extended from its N-terminus by a hexapeptide. Removal of this extension by an endogenous protease generates GLP-1-(7-36)amide, the potent and effective form of the incretin. More recently, comparative endocrinology has contributed to the exploitation of incretins as antidiabetic drugs. Exendin-4, a GLP-1 receptor agonist first isolated from the venom of the Gila monster Heloderma suspectum, is a clinically valuable, long-acting incretin and the skins of several species of frogs synthesize potent insulin-releasing peptides with therapeutic potential.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2971
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 15:05
Last Modified:11 Jun 2010 09:45

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