Recent Progress in the Use of Glucagon and Glucagon Receptor Antago-nists in the Treatment of Diabetes Mellitus

Lotfy , Mohamed; Kalasz , Huba; Szalai , Gyorgy; Singh , Jaipaul; Adeghate , Ernest

Recent Progress in the Use of Glucagon and Glucagon Receptor Antago-nists in the Treatment of Diabetes Mellitus

Mohamed Lotfy ¹, Huba Kalasz ², Gyorgy Szalai ³, Jaipaul Singh ⁴, Ernest Adeghate ^{*, 5}

¹ Department of Biology, College of Science, United Arab Emirates University; School of Forensic and Investigative Sciences, University of Central Lancashire, Preston PR1 2HE, England, UK; National Research Centre, Hormones Department, Cairo, Egypt

² Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary

³ ENT Department, St. Janos Hospital, Budapest, Hungary

⁴ School of Forensic and Investigative Sciences and School of Pharmacy and Biomedical Science, University of Central Lancashire, Preston PR1 2HE, England, UK

⁵ Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Ar-ab Emirates.

Article Information

Identifiers and Pagination:

Year: 2014
Volume: 8
First Page: 28
Last Page: 35
Publisher ID: TOMCJ-8-28
DOI: 10.2174/1874104501408010028

Article History:

Received Date: 6/9/2014
Revision Received Date: 8/10/2014
Acceptance Date: 12/10/2014
Electronic publication date: 31 /12/2014
Collection year: 2014

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© Lotfy et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

^* Address correspondence to this author at the Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates Univer-sity, P.O Box 17666, Al Ain, United Arab Emirates; Tel: +971-3-7137496; Fax: +971-3-7672033; E-mail: eadeghate@uaeu.ac.ae

Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques.

Keyword: Diabetes mellitus, glucagon, glucagon receptor antagonists, pancreas..

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Ernest A. Adeghate

Department of Anatomy
College of Medicine & Health Sciences
UAE University
Al Ain
United Arab Emirates

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RESEARCH ARTICLE

Recent Progress in the Use of Glucagon and Glucagon Receptor Antago-nists in the Treatment of Diabetes Mellitus

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