Abstract
VPAC2P-PEG is a VPAC2 receptor agonist peptide that acts as a glucose-dependent insulin secretagogue. Proteolysis by DPPIV may contribute to the in vivo clearance of VPAC2P-PEG. Here, the N-terminus of VPAC2P-PEG is modified by N-terminal acetylation to impart DPPIV resistance. The acetylated peptide, Ac-VPAC2P-PEG, is a selective and potent VPAC2 agonist, resistant to DPPIV proteolysis, and exhibits substantially improved half-life and glucose disposal in rodents. Ac-VPAC2P-PEG has therapeutic potential for diabetes management.
MeSH terms
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Acetylation
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Dipeptidyl Peptidase 4 / metabolism*
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Glucose / metabolism*
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Half-Life
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Humans
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Hydrolysis
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / pharmacology
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Insulin / metabolism*
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Insulin Secretion
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Male
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Peptides / chemical synthesis*
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Peptides / chemistry
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Peptides / pharmacology
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptors, Vasoactive Intestinal Peptide, Type II / agonists*
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Receptors, Vasoactive Intestinal Peptide, Type II / metabolism
Substances
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Hypoglycemic Agents
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Insulin
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Peptides
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Receptors, Vasoactive Intestinal Peptide, Type II
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Dipeptidyl Peptidase 4
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Glucose