Exchange protein directly activated by cyclic AMP isoform 2 is not a direct target of sulfonylurea drugs.
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.
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Tamara
T
Tsalkova
Alexey V
AV
Gribenko
Xiaodong
X
Cheng
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D005947:Glucose / Q000008:administration & dosage; D005905:Glyburide / Q000378:metabolism / Q000494:pharmacology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014044:Tolbutamide / Q000378:metabolism / Q000494:pharmacology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
D001786:Blood Glucose; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D007004:Hypoglycemic Agents; D007328:Insulin; C486707:Rapgef4 protein, mouse; D013453:Sulfonylurea Compounds; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014044:Tolbutamide; D000242:Cyclic AMP; D020827:rap1 GTP-Binding Proteins; D005947:Glucose; D005905:Glyburide