Abstract
It has been reported by Zhang et al. that antidiabetic sulfonylurea drugs promote insulin secretion by directly binding to exchange protein directly activated by cyclic AMP isoform 2 (Epac2) and activating its down-stream effector Rap1. However, a critical link for an unambiguous validation of a direct interaction between Epac2 and sulfonylurea using purified individual components is missing. Our in vitro analyses using purified full-length Epac2 and Rap1 suggest that sulfonylureas are not able to directly bind to Epac2, nor are they capable of triggering Epac2-dependent Rap1 activation.
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Blood Glucose / analysis
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COS Cells
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Chlorocebus aethiops
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Cyclic AMP / metabolism*
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Fluorescence Resonance Energy Transfer
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Glucose / administration & dosage
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Glyburide / metabolism
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Glyburide / pharmacology
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism*
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / metabolism*
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Hypoglycemic Agents / pharmacology
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Insulin / blood
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Insulin / metabolism
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Insulin Secretion
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Islets of Langerhans / metabolism
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Mice
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Mice, Inbred C57BL
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Sulfonylurea Compounds / chemistry
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Sulfonylurea Compounds / metabolism*
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Sulfonylurea Compounds / pharmacology
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Tolbutamide / metabolism
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Tolbutamide / pharmacology
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rap1 GTP-Binding Proteins / metabolism
Substances
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Blood Glucose
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Carrier Proteins
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Guanine Nucleotide Exchange Factors
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Hypoglycemic Agents
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Insulin
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Rapgef4 protein, mouse
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Sulfonylurea Compounds
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8-Bromo Cyclic Adenosine Monophosphate
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Tolbutamide
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Cyclic AMP
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rap1 GTP-Binding Proteins
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Glucose
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Glyburide