Cyclic AMP sensor EPAC proteins and energy homeostasis

被引：61

作者：

Almahariq, Muayad ^{[1
]}

Mei, Fang C. ^{[1
,2
]}

Cheng, Xiaodong ^{[1
,2
]}

机构：

[1] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA

[2] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2014年 / 25卷 / 02期

基金：

美国国家卫生研究院;

关键词：

exchange protein directly activated by cAMP (EPAC); cAMP; energy balance; insulin secretion; leptin resistance; GLUCAGON-LIKE PEPTIDE-1; PROGLUCAGON GENE-EXPRESSION; SELECTIVE CAMP ANALOG; PANCREATIC BETA-CELLS; RAT INS-1 CELLS; STIMULATED INSULIN-SECRETION; GLUCOSE-HOMEOSTASIS; SIGNALING PATHWAYS; LEPTIN RESISTANCE; KINASE-A;

D O I：

10.1016/j.tem.2013.10.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：60 / 71

页数：12

共 108 条

[41] Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve [J].

German, Jonathan ;

Kim, Francis ;

Schwartz, Gary J. ;

Havel, Peter J. ;

Rhodes, Christopher J. ;

Schwartz, Michael W. ;

Morton, Gregory J. .

ENDOCRINOLOGY, 2009, 150 (10) :4502-4511

[42] Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia [J].

German, Jonathan P. ;

Thaler, Joshua P. ;

Wisse, Brent E. ;

Oh-I, Shinsuke ;

Sarruf, David A. ;

Matsen, Miles E. ;

Fischer, Jonathan D. ;

Taborsky, Gerald J., Jr. ;

Schwartz, Michael W. ;

Morton, Gregory J. .

ENDOCRINOLOGY, 2011, 152 (02) :394-404

[43] Epac: Defining a New Mechanism for cAMP Action [J].

Gloerich, Martijn ;

Bos, Johannes L. .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2010, 50 :355-375

[44] Off-target effect of the Epac agonist 8-pCPT-2′-O-Me-cAMP on P2Y12 receptors in blood platelets [J].

Herfindal, Lars ;

Nygaard, Gyrid ;

Kopperud, Reidun ;

Krakstad, Camilla ;

Doskeland, Stein Ove ;

Selheim, Frode .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 437 (04) :603-608

[45] DNA Methylation of Alternative Promoters Directs Tissue Specific Expression of Epac2 Isoforms [J].

Hoivik, Erling A. ;

Witsoe, Solveig L. ;

Bergheim, Inger R. ;

Xu, Yunjian ;

Jakobsson, Ida ;

Tengholm, Anders ;

Doskeland, Stein Ove ;

Bakke, Marit .

PLOS ONE, 2013, 8 (07)

[46] Epac-selective cAMP analogs: New tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors [J].

Holz, George G. ;

Chepurny, Oleg G. ;

Schwede, Frank .

CELLULAR SIGNALLING, 2008, 20 (01) :10-20

[47] Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons [J].

Huo, Lihong ;

Gamber, Kevin ;

Greeley, Sarah ;

Silva, Jose ;

Huntoon, Nicholas ;

Leng, Xing-Hong ;

Bjorbaek, Christian .

CELL METABOLISM, 2009, 9 (06) :537-547

[48] Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic α- and intestinal L-cell lines [J].

Islam, Diana ;

Zhang, Nina ;

Wang, Peixiang ;

Li, Hang ;

Brubaker, Patricia L. ;

Gaisano, Herbert Y. ;

Wang, Qinghua ;

Jin, Tianru .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2009, 296 (01) :E174-E181

[49] Potentiation of Sulfonylurea Action by an EPAC-selective cAMP Analog in INS-1 Cells: Comparison of Tolbutamide and Gliclazide and a Potential Role for EPAC Activation of a 2-APB-sensitive Ca2+ Influx [J].

Jarrard, Rachel E. ;

Wang, Yuchen ;

Salyer, Amy E. ;

Pratt, Evan P. S. ;

Soderling, Ian M. ;

Guerra, Marcy L. ;

Lange, Allison M. ;

Broderick, Hilary J. ;

Hockerman, Gregory H. .

MOLECULAR PHARMACOLOGY, 2013, 83 (01) :191-205

[50] Mechanisms underlying proglucagon gene expression [J].

Jin, Tianru .

JOURNAL OF ENDOCRINOLOGY, 2008, 198 (01) :17-28

← 1 2 3 4 5 6 7 8 9 10 →