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Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

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Affiliated Author(s)
박재형송대규
Alternative Author(s)
Park, Jae HyungSong, Dae Kyu
Journal Title
Diabetes
ISSN
0012-1797
Issued Date
2015
Abstract
Incretin-related drugs and sulfonylureas are currently used worldwide for the treatment of type 2 diabetes. We recently found that Epac2A, a cAMP binding protein having guanine nucleotide exchange activity toward Rap, is a target of both incretin and sulfonylurea. This suggests the possibility of interplay between incretin and sulfonylurea through Epac2A/Rap1 signaling in insulin secretion. In this study, we examined the combinatorial effects of incretin and various sulfonylureas on insulin secretion and activation of Epac2A/Rap1 signaling. A strong augmentation of insulin secretion by combination of GLP-1 and glibenclamide or glimepiride, which was found in Epac2A+/+ mice, was markedly reduced in Epac2A−/− mice. In contrast, the combinatorial effect of GLP-1 and gliclazide was rather mild, and the effect was not altered by Epac2A ablation. Activation of Rap1 was enhanced by the combination of an Epac-selective cAMP analog with glibenclamide or glimepiride but not gliclazide. In diet-induced obese mice, ablation of Epac2A reduced the insulin secretory response to coadministration of the GLP-1 receptor agonist liraglutide and glimepiride. These findings clarify the critical role of Epac2A/Rap1 signaling in the augmenting effect of incretin and sulfonylurea on insulin secretion and provide the basis for the effects of combination therapies of incretin-related drugs and sulfonylureas.
Department
Dept. of Physiology (생리학)
Publisher
School of Medicine
Citation
Harumi Takahashi et al. (2015). Role of Epac2A/Rap1 Signaling
in Interplay Between Incretin
and Sulfonylurea in Insulin
Secretion. Diabetes, 64(4), 1262–1272. doi: 10.2337/db14-0576
Type
Article
ISSN
0012-1797
DOI
10.2337/db14-0576
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35566
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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