Abstract
Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by alpha2,6-sialyltransferase (alpha2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-Ins(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Amino Acid Sequence
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Animals
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Blood Glucose / drug effects
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Blood Glucose / metabolism
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Glutamine / chemistry
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Glutamine / metabolism
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Glycoproteins / chemical synthesis*
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Glycoproteins / chemistry
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Glycoproteins / metabolism
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Glycoproteins / pharmacology*
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Glycosylation
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Humans
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Insulin / analogs & derivatives*
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Insulin / chemical synthesis
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Insulin / metabolism
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Insulin / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Mutagenesis
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Oligosaccharides / chemical synthesis*
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Oligosaccharides / chemistry
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Oligosaccharides / pharmacology*
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Protein Conformation
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Receptor, Insulin / metabolism
Substances
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Blood Glucose
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Glycoproteins
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Insulin
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Oligosaccharides
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sialooligosaccharides
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Glutamine
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Receptor, Insulin