Abstract
Objectives:
The aim of this study was to characterize the conformation and potency of a mutated glucagon-like peptide-1 (mGLP-1), and evaluate its glucose-lowering activity in diabetic mice.
Methods:
Spectroscopy techniques were employed to characterize the conformation of mGLP-1. Glucose tolerance test was performed to determine the potency of mGLP-1 in vivo. A mouse model in which diabetes was induced by multiple low doses of streptozotocin was established to evaluate the glucose-lowering activity of mGLP-1.
Key findings:
Compared with native GLP-1, mGLP-1 had a similar conformation and an enhanced potency in vivo. In diabetic mice, mGLP-1 displayed a significantly improved glucose-lowering activity as judged by fasting glucose and insulin, oral glucose tolerance test, beta cell function analysis and histochemical analysis.
Conclusions:
Collectively, mGLP-1 possesses an improved glucose-lowering activity in vivo and therefore can be recognized as a potential candidate for the future development of anti-diabetic drugs.
© 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Animals
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / pathology
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Diabetes Mellitus, Experimental / physiopathology
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Drug Design*
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Glucagon-Like Peptide 1 / administration & dosage
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Glucagon-Like Peptide 1 / chemistry
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Glucagon-Like Peptide 1 / genetics
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Glucagon-Like Peptide 1 / therapeutic use*
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Glucose Tolerance Test
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Hyperglycemia / prevention & control*
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / adverse effects
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / therapeutic use*
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Injections, Intraperitoneal
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Insulin / blood
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Insulin / metabolism
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Insulin Resistance
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Insulin Secretion
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Insulin-Secreting Cells / drug effects*
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Insulin-Secreting Cells / metabolism
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Insulin-Secreting Cells / pathology
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Kidney / drug effects
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Kidney / pathology
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Liver / drug effects
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Liver / pathology
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Male
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Mice
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Mice, Inbred Strains
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Mutant Proteins / administration & dosage
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Mutant Proteins / adverse effects
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Mutant Proteins / chemistry
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Mutant Proteins / therapeutic use*
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Protein Conformation
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / adverse effects
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Recombinant Proteins / chemistry
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Recombinant Proteins / therapeutic use
Substances
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Hypoglycemic Agents
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Insulin
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Mutant Proteins
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Recombinant Proteins
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Glucagon-Like Peptide 1