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Literature DB >> 24231725

Cyclic AMP sensor EPAC proteins and energy homeostasis.

Muayad Almahariq¹, Fang C Mei², Xiaodong Cheng³.

Abstract

The pleiotropic second-messenger cAMP plays a crucial role in mediating the effects of various hormones on metabolism. The major intracellular functions of cAMP are transduced by protein kinase A (PKA) and by exchange proteins directly activated by cAMP (EPACs). The latter act as guanine-nucleotide exchange factors for the RAS-like small G proteins Rap1 and Rap2. Although the role of PKA in regulating energy balance has been extensively studied, the impact of EPACs remains relatively enigmatic. This review summarizes recent genetic and pharmacological studies concerning EPAC involvement in glucose homeostasis and energy balance via the regulation of leptin and insulin signaling pathways. In addition, the development of small-molecule EPAC-specific modulators and their therapeutic potential for the treatment of diabetes and obesity are discussed.

Entities: CellLine Chemical Disease Gene Species

Keywords: cAMP; energy balance; exchange protein directly activated by cAMP (EPAC); insulin secretion; leptin resistance

Mesh：

Substances：

Year: 2013 PMID： 24231725 PMCID： PMC3946731 DOI： 10.1016/j.tem.2013.10.004

Source DB: PubMed Journal: Trends Endocrinol Metab ISSN： 1043-2760 Impact factor: 12.015

107 in total

1. Facilitation of ß-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac.

Authors: Colin A Leech; Igor Dzhura; Oleg G Chepurny; Frank Schwede; Hans-G Genieser; George G Holz
Journal: Islets Date: 2010 Mar-Apr Impact factor: 2.694

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3. Profile of Brian K. Kobilka and Robert J. Lefkowitz, 2012 Nobel laureates in chemistry.

Authors: Richard B Clark
Journal: Proc Natl Acad Sci U S A Date: 2013-02-14 Impact factor: 11.205

4. 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP.

Authors: Haijun Chen; Tamara Tsalkova; Fang C Mei; Yaohua Hu; Xiaodong Cheng; Jia Zhou
Journal: Bioorg Med Chem Lett Date: 2012-04-26 Impact factor: 2.823

Review 5. Mechanisms of action of glucagon-like peptide 1 in the pancreas.

Authors: Máire E Doyle; Josephine M Egan
Journal: Pharmacol Ther Date: 2006-12-28 Impact factor: 12.310

Review 6. cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration.

Authors: Rebecca Berdeaux; Randi Stewart
Journal: Am J Physiol Endocrinol Metab Date: 2012-02-21 Impact factor: 4.310

7. cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells.

Authors: Guoxin Kang; Oleg G Chepurny; Brian Malester; Michael J Rindler; Holger Rehmann; Johannes L Bos; Frank Schwede; William A Coetzee; George G Holz
Journal: J Physiol Date: 2006-04-13 Impact factor: 5.182

8. POU homeodomain protein Oct-1 functions as a sensor for cyclic AMP.

Authors: Peixiang Wang; Qinghua Wang; Jane Sun; Jing Wu; Hang Li; Nina Zhang; Yachi Huang; Brenda Su; Ren-ke Li; Ling Liu; Yi Zhang; Harry P Elsholtz; Jim Hu; Herbert Y Gaisano; Tianru Jin
Journal: J Biol Chem Date: 2009-07-18 Impact factor: 5.157

9. Positional cloning of the mouse obese gene and its human homologue.

Authors: Y Zhang; R Proenca; M Maffei; M Barone; L Leopold; J M Friedman
Journal: Nature Date: 1994-12-01 Impact factor: 49.962

10. Pancreatic β-cell response to increased metabolic demand and to pharmacologic secretagogues requires EPAC2A.

Authors: Woo-Jin Song; Prosenjit Mondal; Yuanyuan Li; Suh Eun Lee; Mehboob A Hussain
Journal: Diabetes Date: 2013-04-11 Impact factor: 9.461

38 in total

1. Glucagon and Insulin Cooperatively Stimulate Fibroblast Growth Factor 21 Gene Transcription by Increasing the Expression of Activating Transcription Factor 4.

Authors: Kimberly M Alonge; Gordon P Meares; F Bradley Hillgartner
Journal: J Biol Chem Date: 2017-02-10 Impact factor: 5.157

2. Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1.

Authors: Pooja Singhmar; XiaoJiao Huo; Niels Eijkelkamp; Susana Rojo Berciano; Faiza Baameur; Fang C Mei; Yingmin Zhu; Xiaodong Cheng; David Hawke; Federico Mayor; Cristina Murga; Cobi J Heijnen; Annemieke Kavelaars
Journal: Proc Natl Acad Sci U S A Date: 2016-02-29 Impact factor: 11.205

3. Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes.

Authors: Jung Hyun Lee; Ji Seul Han; Jinuk Kong; Yul Ji; Xuchao Lv; Junho Lee; Peng Li; Jae Bum Kim
Journal: J Biol Chem Date: 2016-08-04 Impact factor: 5.157

Review 4. Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.

Authors: William G Robichaux; Xiaodong Cheng
Journal: Physiol Rev Date: 2018-04-01 Impact factor: 37.312

5. Pharmacological inhibition and genetic knockdown of exchange protein directly activated by cAMP 1 reduce pancreatic cancer metastasis in vivo.

Authors: Muayad Almahariq; Celia Chao; Fang C Mei; Mark R Hellmich; Igor Patrikeev; Massoud Motamedi; Xiaodong Cheng
Journal: Mol Pharmacol Date: 2014-11-10 Impact factor: 4.436

Review 6. Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC).

Authors: Haijun Chen; Christopher Wild; Xiaobin Zhou; Na Ye; Xiaodong Cheng; Jia Zhou
Journal: J Med Chem Date: 2013-11-27 Impact factor: 7.446

10. Exchange protein directly activated by cAMP (Epac) 1 plays an essential role in stress-induced exercise capacity by regulating PGC-1α and fatty acid metabolism in skeletal muscle.

Authors: Wai-Kin So; Hyoung Kyu Kim; Yingxian Chen; Seung Hun Jeong; Patrick Ka Kit Yeung; Billy C K Chow; Jin Han; Sookja K Chung
Journal: Pflugers Arch Date: 2020-01-18 Impact factor: 3.657