Abstract
p-Boronophenylmethoxycarbonyl (BPmoc) is a protecting group for amines that is removable by treatment with hydrogen peroxide (H2O2). We prepared BPmoc-modified insulin (BPmoc-Ins) and subcutaneously injected the formulation into diabetic rats. The results demonstrated that BPmoc effectively sealed the blood glucose (Glc)-lowering effects of Ins. Conversely, coinjection of BPmoc-Ins and Glc oxidase (GOx) resulted in reduced blood Glc levels, indicating that Ins was generated from BPmoc-Ins through the following reactions: oxidation of endogenous Glc by GOx; production of H2O2 accompanied by Glc oxidation; removal of BPmoc residues by H2O2. These results show the potential of BPmoc-Ins for a Glc-responsive Ins release system.
Keywords:
boronic acid; glucose-responsive release; hydrogen peroxide; hypoglycemia; insulin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Glucose / analysis
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Blood Glucose / chemistry
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Blood Glucose / drug effects*
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Boronic Acids / chemistry
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Delayed-Action Preparations / administration & dosage
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Delayed-Action Preparations / chemistry
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Delayed-Action Preparations / pharmacokinetics
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Diabetes Mellitus, Type 2 / blood
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Diabetes Mellitus, Type 2 / drug therapy*
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Disease Models, Animal
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Drug Liberation
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Glucose Oxidase / metabolism
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Humans
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Hydrogen Peroxide / chemistry*
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Hydrogen Peroxide / metabolism
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Injections, Subcutaneous
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Insulin, Regular, Human / administration & dosage*
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Insulin, Regular, Human / chemistry
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Insulin, Regular, Human / pharmacokinetics
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Oxidation-Reduction
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Rats
Substances
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Blood Glucose
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Boronic Acids
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Delayed-Action Preparations
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Insulin, Regular, Human
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Hydrogen Peroxide
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Glucose Oxidase