계명대학교 의학도서관 Repository

Glucagon-Like Peptide-1 Enhances Glucokinase Activity in Pancreatic β-Cells through the Association of Epac2 with Rim2 and Rab3A

Metadata Downloads
Author(s)
Jae-Hyung ParkSun-Joo KimSung-Hee ParkDae-Gu SonJae-Hoon BaeHyoung Kyu KimJin HanDae-Kyu Song
Keimyung Author(s)
Park, Jae HyungBae, Jae HoonSong, Dae Kyu
Department
Dept. of Physiology (생리학)
Dept. of Plastic Surgery (성형외과학)
Journal Title
Endocrinology
Issued Date
2012
Volume
153
Issue
2
Abstract
Glucokinase (GK), which phosphorylates D-glucose, is a major glucose sensor in -cells for glucosestimulated
insulin secretion (GSIS) and is a promising new drug target for type 2 diabetes (T2D). In
T2D, pancreatic -cells exhibit defective glucose sensitivity, which leads to impaired GSIS. Although
glucagon-like peptide-1-(7–36)-amide (GLP-1) is known to enhance -cell glucose sensitivity, the
effect of GLP-1 on GK activity is still unknown. The present study demonstrated that GLP-1 pretreatment
for 30 min significantly enhanced GK activity in a glucose-dependent manner, with a
lower Michaelis-Menten constant (Km) but unchanged maximal velocity (Vmax). Thus, GLP-1 acutely
enhanced cellular glucose uptake, mitochondrial membrane potential, and cellular ATP levels in
response to glucose in rat INS-1 and native -cells. This effect of GLP-1 occurred via its G proteincoupled
receptor pathway in a cAMP-dependent but protein kinase A-independent manner with
evidence of exchange protein activated by cAMP (Epac) involvement. Silencing Epac2, interacting
molecule of the small G protein Rab3 (Rim2), or Ras-associated protein Rab3A (Rab3A) significantly
blocked the effect of GLP-1. These results suggested that GLP-1 can further potentiate GSIS by enhancing
GK activity through the signaling of Epac2 to Rim2 and Rab3A, which is the similar pathway
for GLP-1 to potentiate Ca2 -dependent insulin granule exocytosis. The present findingmayalso be an
important mechanism of GLP-1 for recovery of GSIS in T2D. (Endocrinology 153: 574–582, 2012)
Keimyung Author(s)(Kor)
박재형
배재훈
송대규
Publisher
School of Medicine
Citation
Jae-Hyung Park et al. (2012). Glucagon-Like Peptide-1 Enhances Glucokinase Activity in Pancreatic β-Cells through the Association of Epac2 with Rim2 and Rab3A. Endocrinology, 153(2), 574–582. doi: 10.1210/en.2011-0259
Type
Article
ISSN
0013-7227
DOI
10.1210/en.2011-0259
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35625
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. School of Medicine (의과대학) > Dept. of Plastic Surgery (성형외과학)
공개 및 라이선스
  • 공개 구분공개
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.