Abstract
Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake. In agreement with these actions, it has been shown to be highly effective in the treatment of Type 2 diabetes, causing marked improvements in glycaemic profile, insulin sensitivity and beta-cell performance, as well as weight reduction. The hormone is metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and, therefore, cannot be easily used clinically. Instead, resistant analogues of the hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV inhibitors, which have been demonstrated to protect the endogenous hormone and enhance its activity. Agonists include both albumin-bound analogues of GLP-1 and exendin-4, a lizard peptide. Clinical studies with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation, therefore, appears very promising.
MeSH terms
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Adenosine Deaminase / physiology
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Adenosine Deaminase Inhibitors*
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Afferent Pathways / physiology
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Animals
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Appetite / drug effects
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / physiopathology
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Dipeptidyl Peptidase 4 / physiology
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Drug Therapy, Combination
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Exenatide
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Glucagon / agonists
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Glucagon / analogs & derivatives*
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Glucagon / metabolism
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Glucagon / pharmacology
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Glucagon / physiology*
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Glucagon / therapeutic use
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Glucagon-Like Peptide 1
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Glucagon-Like Peptide-1 Receptor
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Glycoproteins / antagonists & inhibitors*
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Glycoproteins / physiology
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Humans
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / pharmacology
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Hypoglycemic Agents / therapeutic use*
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Hypothalamus / drug effects
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Hypothalamus / physiopathology
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Insulin / biosynthesis
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Insulin / genetics
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Insulin / metabolism
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Insulin Secretion
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Intestinal Mucosa / innervation
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Intestinal Mucosa / metabolism
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Islets of Langerhans / drug effects
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Islets of Langerhans / metabolism
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Liraglutide
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Lizards
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Maleimides / therapeutic use
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Mice
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Mice, Knockout
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Mice, Obese
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Peptide Fragments / agonists
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Peptide Fragments / physiology*
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Peptides / pharmacology
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Peptides / therapeutic use
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Proglucagon
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Protein Precursors / agonists
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Protein Precursors / metabolism
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Protein Precursors / pharmacology
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Protein Precursors / physiology*
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Rats
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Rats, Zucker
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Receptors, Glucagon / agonists*
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Receptors, Glucagon / deficiency
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Receptors, Glucagon / physiology
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Venoms / pharmacology
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Venoms / therapeutic use
Substances
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Adenosine Deaminase Inhibitors
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CJC 1131
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GLP1R protein, human
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Glp1r protein, mouse
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Glp1r protein, rat
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Glucagon-Like Peptide-1 Receptor
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Glycoproteins
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Hypoglycemic Agents
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Insulin
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Maleimides
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Peptide Fragments
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Peptides
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Protein Precursors
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Receptors, Glucagon
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Venoms
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Proglucagon
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Liraglutide
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Glucagon-Like Peptide 1
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Glucagon
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Exenatide
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DPP4 protein, human
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Dipeptidyl Peptidase 4
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Adenosine Deaminase