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

Lotfy M, Kalasz H, Szalai G, Singh J, Adeghate E - Open Med Chem J (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Effects of either glucagon or glucagon receptor antagonist on reduction of diabetic complications.Fig. (2). shows how a schematic diagram of interaction between glucagon, glucagon antagonist, glucagon receptor antagonist and glycogenolysisin the regulation of blood glucose level. (-) = inhibition, = ↓↓reduction.
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Figure 2: Effects of either glucagon or glucagon receptor antagonist on reduction of diabetic complications.Fig. (2). shows how a schematic diagram of interaction between glucagon, glucagon antagonist, glucagon receptor antagonist and glycogenolysisin the regulation of blood glucose level. (-) = inhibition, = ↓↓reduction.

Mentions: This mini-review has shed light on the role of glucagon in the regulation of glucose metabolism and how it could be used as a tool for the treatment of DM either by using antagonists or gene knockout techniques that could neutralize the action of glucagon or blocking the binding of glucagon to its receptors with antibody immunization (Fig. 2 and Table 3) A summary of the efficacy, dosage, adverse effect and the status of some glucagon receptor antagonists is given in Table 4.


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

Lotfy M, Kalasz H, Szalai G, Singh J, Adeghate E - Open Med Chem J (2014)

Effects of either glucagon or glucagon receptor antagonist on reduction of diabetic complications.Fig. (2). shows how a schematic diagram of interaction between glucagon, glucagon antagonist, glucagon receptor antagonist and glycogenolysisin the regulation of blood glucose level. (-) = inhibition, = ↓↓reduction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321206&req=5

Figure 2: Effects of either glucagon or glucagon receptor antagonist on reduction of diabetic complications.Fig. (2). shows how a schematic diagram of interaction between glucagon, glucagon antagonist, glucagon receptor antagonist and glycogenolysisin the regulation of blood glucose level. (-) = inhibition, = ↓↓reduction.
Mentions: This mini-review has shed light on the role of glucagon in the regulation of glucose metabolism and how it could be used as a tool for the treatment of DM either by using antagonists or gene knockout techniques that could neutralize the action of glucagon or blocking the binding of glucagon to its receptors with antibody immunization (Fig. 2 and Table 3) A summary of the efficacy, dosage, adverse effect and the status of some glucagon receptor antagonists is given in Table 4.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus