The Journal of pharmacy and pharmacology · 2012
A mutated glucagon-like peptide-1 with improved glucose-lowering activity in diabetic mice.
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Gao Mingming, Tong Yue, Gao Xiangdong, Yao Wenbing
Аннотация
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.
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.
Предметные рубрики MeSH
Amino Acid SubstitutionAnimalsDiabetes Mellitus, ExperimentalDrug DesignGlucagon-Like Peptide 1Glucose Tolerance TestHyperglycemiaHypoglycemic AgentsInjections, IntraperitonealInsulinInsulin ResistanceInsulin SecretionInsulin-Secreting CellsKidneyLiverMaleMiceMice, Inbred StrainsMutant ProteinsProtein ConformationRecombinant Proteins