Cyclic AMP sensor EPAC proteins and energy homeostasis

Trends in Endocrinology and Metabolism

Volumn 25, Issue 2, 2014, Pages 60-71

  Almahariq, Muayad ^a   Mei, Fang C ^a,b   Cheng, Xiaodong ^a,b  

^a University of Texas Medical Branch School of Medicine   (United States)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

CAMP; Energy balance; Exchange protein directly activated by cAMP (EPAC); Insulin secretion; Leptin resistance

Indexed keywords

ANTIPORTER; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; EXCHANGE PROTEIN DIRECTLY ACTIVATED BY CYCLIC AMP; GUANINE NUCLEOTIDE EXCHANGE FACTOR; INSULIN; LEPTIN; UNCLASSIFIED DRUG;

ENERGY BALANCE; GLUCOSE HOMEOSTASIS; INSULIN RELEASE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION;

CAMP; ENERGY BALANCE; EXCHANGE PROTEIN DIRECTLY ACTIVATED BY CAMP (EPAC); INSULIN SECRETION; LEPTIN RESISTANCE;

ANIMALS; CYCLIC AMP; CYCLIC AMP-DEPENDENT PROTEIN KINASES; ENERGY METABOLISM; GLUCOSE; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HOMEOSTASIS; HUMANS; INSULIN; LEPTIN; MODELS, ANIMAL; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS;

EID: 84892955099     PISSN: 10432760     EISSN: 18793061     Source Type: Journal    
DOI: 10.1016/j.tem.2013.10.004     Document Type: Review

References (108)

1. Berthet J., et al. The relationship of epinephrine and glucagon to liver phosphorylase. IV. Effect of epinephrine and glucagon on the reactivation of phosphorylase in liver homogenates. J. Biol. Chem. 1957, 224:463-475.
2. Clark R.B. Profile of Brian K. Kobilka and Robert J. Lefkowitz, 2012 Nobel laureates in chemistry. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:5274-5275.
3. Beavo J.A., Brunton L.L. Cyclic nucleotide research - still expanding after half a century. Nat. Rev. Mol. Cell Biol. 2002, 3:710-718.
4. Craven K.B., Zagotta W.N. CNG and HCN channels: two peas, one pod. Annu. Rev. Physiol. 2006, 68:375-401.
5. de Rooij J., et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 1998, 396:474-477.
6. Kawasaki H., et al. A family of cAMP-binding proteins that directly activate Rap1. Science 1998, 282:2275-2279.
7. Cheng X., et al. Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim. Biophys. Sin. (Shanghai) 2008, 40:651-662.
8. Mei F.C., et al. Differential signaling of cyclic AMP: opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B activation. J. Biol. Chem. 2002, 277:11497-11504.
9. Schmidt M., et al. Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol. Rev. 2013, 65:670-709.
10. Gloerich M., Bos J.L. Epac: defining a new mechanism for cAMP action. Annu. Rev. Pharmacol. Toxicol. 2010, 50:355-375.
11. Malik V.S., et al. Global obesity: trends, risk factors and policy implications. Nat. Rev. Endocrinol. 2013, 9:13-27.
12. Zhang Y., et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432.
13. Gautron L., Elmquist J.K. Sixteen years and counting: an update on leptin in energy balance. J. Clin. Invest. 2011, 121:2087-2093.
14. Baumann H., et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:8374-8378.
15. Vaisse C., et al. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat. Genet. 1996, 14:95-97.
16. Niswender K.D., et al. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 2001, 413:794-795.
17. Al-Qassab H., et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab. 2009, 10:343-354.
18. Myers M.G., et al. Mechanisms of leptin action and leptin resistance. Annu. Rev. Physiol. 2008, 70:537-556.
19. Morris D.L., Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am. J. Physiol. Endocrinol. Metab. 2009, 297:E1247-E1259.
20. Madsen L., Kristiansen K. The importance of dietary modulation of cAMP and insulin signaling in adipose tissue and the development of obesity. Ann. N. Y. Acad. Sci. 2010, 1190:1-14.
21. Cummings D.E., et al. Genetically lean mice result from targeted disruption of the RII beta subunit of protein kinase A. Nature 1996, 382:622-626.
22. Fukuda M., et al. Induction of leptin resistance by activation of cAMP-Epac signaling. Cell Metab. 2011, 13:331-339.
23. Yan J., et al. Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1. Mol. Cell. Biol. 2013, 33:918-926.
24. Borland G., et al. Activation of protein kinase Calpha by EPAC1 is required for the ERK- and CCAAT/enhancer-binding protein beta-dependent induction of the SOCS-3 gene by cyclic AMP in COS1 cells. J. Biol. Chem. 2009, 284:17391-17403.
25. Williams J.J., Palmer T.M. Unbiased identification of substrates for the Epac1-inducible E3 ubiquitin ligase component SOCS-3. Biochem. Soc. Trans. 2012, 40:215-218.
26. Chua S. Signal transduction pathways for leptin: an embarrassment of riches. Diabetes 2009, 58:513-514.
27. Banno R., et al. PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice. J. Clin. Invest. 2010, 120:720-734.
28. Krajewska M., et al. Development of diabesity in mice with neuronal deletion of Shp2 tyrosine phosphatase. Am. J. Pathol. 2008, 172:1312-1324.
29. Sahu A. Intracellular leptin-signaling pathways in hypothalamic neurons: the emerging role of phosphatidylinositol-3 kinase-phosphodiesterase-3B-cAMP pathway. Neuroendocrinology 2011, 93:201-210.
30. Wilson L.S., et al. A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. J. Biol. Chem. 2011, 286:16285-16296.
31. Omar B., et al. Regulation of AMP-activated protein kinase by cAMP in adipocytes: roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis. Cell. Signal. 2009, 21:760-766.
32. Petersen R.K., et al. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Mol. Cell. Biol. 2008, 28:3804-3816.
33. Brennesvik E.O., et al. Adrenaline potentiates insulin-stimulated PKB activation via cAMP and Epac: implications for cross talk between insulin and adrenaline. Cell. Signal. 2005, 17:1551-1559.
34. Baviera A.M., et al. Involvement of cAMP/Epac/PI3K-dependent pathway in the antiproteolytic effect of epinephrine on rat skeletal muscle. Mol. Cell. Endocrinol. 2010, 315:104-112.
35. Park S.J., et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 2012, 148:421-433.
36. Knight Z.A., Shokat K.M. Chemical genetics: where genetics and pharmacology meet. Cell 2007, 128:425-430.
37. Kai A.K., et al. Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome. FASEB J. 2013, 27:4122-4135.
38. Straub S.G., Sharp G.W. Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab. Res. Rev. 2002, 18:451-463.
39. Doyle M.E., Egan J.M. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol. Ther. 2007, 113:546-593.
40. Vliem M.J., et al. 8-pCPT-2'-O-Me-cAMP-AM: an improved Epac-selective cAMP analogue. Chembiochem 2008, 9:2052-2054.
41. Kelley G.G., et al. Glucose-dependent potentiation of mouse islet insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM. Islets 2009, 1:260-265.
42. Chepurny O.G., et al. Enhanced Rap1 activation and insulin secretagogue properties of an acetoxymethyl ester of an Epac-selective cyclic AMP analog in rat INS-1 cells: studies with 8-pCPT-2'-O-Me-cAMP-AM. J. Biol. Chem. 2009, 284:10728-10736.
43. Chepurny O.G., et al. PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of Langerhans. Am. J. Physiol. Endocrinol. Metab. 2010, 298:E622-E633.
44. Song W.J., et al. Pancreatic β-cell response to increased metabolic demand and to pharmacologic secretagogues requires EPAC2A. Diabetes 2013, 62:2796-2807.
45. Andrikopoulos S., et al. Evaluating the glucose tolerance test in mice. Am. J. Physiol. Endocrinol. Metab. 2008, 295:E1323-E1332.
46. Ahrén B., et al. The augmenting effect on insulin secretion by oral versus intravenous glucose is exaggerated by high-fat diet in mice. J. Endocrinol. 2008, 197:181-187.
47. Zhang C.L., et al. The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. Science 2009, 325:607-610.
48. Hoivik E.A., et al. DNA methylation of alternative promoters directs tissue specific expression of Epac2 isoforms. PLoS ONE 2013, 8:e67925.
49. Moon M.J., et al. Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1. Mol. Cells 2011, 32:389-395.
50. Kemp D.M., Habener J.F. Insulinotropic hormone glucagon-like peptide 1 (GLP-1) activation of insulin gene promoter inhibited by p38 mitogen-activated protein kinase. Endocrinology 2001, 142:1179-1187.
51. Garber A.J. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care 2011, 34(Suppl. 2):S279-S284.
52. Jin T. Mechanisms underlying proglucagon gene expression. J. Endocrinol. 2008, 198:17-28.
53. Lotfi S., et al. Role of the exchange protein directly activated by cyclic adenosine 5'-monophosphate (Epac) pathway in regulating proglucagon gene expression in intestinal endocrine L cells. Endocrinology 2006, 147:3727-3736.
54. Islam D., et al. Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic alpha- and intestinal L-cell lines. Am. J. Physiol. Endocrinol. Metab. 2009, 296:E174-E181.
55. Dalvi P.S., et al. Direct regulation of the proglucagon gene by insulin, leptin, and cAMP in embryonic versus adult hypothalamic neurons. Mol. Endocrinol. 2012, 26:1339-1355.
56. Wang P., et al. POU homeodomain protein Oct-1 functions as a sensor for cyclic AMP. J. Biol. Chem. 2009, 284:26456-26465.
57. Chepurny O.G., et al. Stimulation of proglucagon gene expression by human GPR119 in enteroendocrine L-cell line GLUTag. Mol. Endocrinol. 2013, 27:1267-1282.
58. Tsalkova T., et al. Isoform-specific antagonists of exchange proteins directly activated by cAMP. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:18613-18618.
59. Tsalkova T., et al. A fluorescence-based high-throughput assay for the discovery of exchange protein directly activated by cyclic AMP (EPAC) antagonists. PLoS ONE 2012, 7:e30441.
60. Almahariq M., et al. A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol. Pharmacol. 2013, 83:122-128.
61. Courilleau D., et al. Identification of a tetrahydroquinoline analog as a pharmacological inhibitor of the cAMP-binding protein Epac. J. Biol. Chem. 2012, 287:44192-44202.
62. Amitani M., et al. The role of leptin in the control of insulin-glucose axis. Front. Neurosci. 2013, 7:51.
63. Coppari R., et al. The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metab. 2005, 1:63-72.
64. Huo L., et al. Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab. 2009, 9:537-547.
65. Koch C., et al. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity. J. Neurosci. 2010, 30:16180-16187.
66. German J., et al. Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve. Endocrinology 2009, 150:4502-4511.
67. German J.P., et al. Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology 2011, 152:394-404.
68. Seufert J. Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 2004, 53(Suppl. 1):S152-S158.
69. Park J.Y., et al. Type 1 diabetes associated with acquired generalized lipodystrophy and insulin resistance: the effect of long-term leptin therapy. J. Clin. Endocrinol. Metab. 2008, 93:26-31.
70. Moon H.S., et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes 2011, 60:1647-1656.
71. Del Prato S., Tiengo A. The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab. Res. Rev. 2001, 17:164-174.
72. Rehmann H. Epac2: a sulfonylurea receptorα. Biochem. Soc. Trans. 2012, 40:6-10.
73. D'Alessio D. The role of dysregulated glucagon secretion in type 2 diabetes. Diabetes Obes. Metab. 2011, 13(Suppl. 1):126-132.
74. Ozaki N., et al. cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat. Cell Biol. 2000, 2:805-811.
75. Rehmann H., et al. Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state. Nature 2006, 439:625-628.
76. Niimura M., et al. Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its subcellular localization and function. J. Cell. Physiol. 2009, 219:652-658.
77. Rehmann H., et al. Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B. Nature 2008, 455:124-127.
78. Yu S., et al. Dissecting the mechanism of Epac activation via hydrogen-deuterium exchange FT-IR and structural modeling. Biochemistry 2006, 45:15318-15326.
79. Li S., et al. Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS). J. Biol. Chem. 2011, 286:17889-17897.
80. White M.A., et al. Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP. PLoS ONE 2012, 7:e49932.
81. Selvaratnam R., et al. cAMP-dependent allostery and dynamics in Epac: an NMR view. Biochem. Soc. Trans. 2012, 40:219-223.
82. Tsalkova T., et al. Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities. J. Biol. Chem. 2009, 284:23644-23651.
83. Kahn B.B., Flier J.S. Obesity and insulin resistance. J. Clin. Invest. 2000, 106:473-481.
84. Berdeaux R., Stewart R. cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration. Am. J. Physiol. Endocrinol. Metab. 2012, 303:E1-E17.
85. O'Neill H.M., et al. AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity. Mol. Cell. Endocrinol. 2013, 366:135-151.
86. Kang G., et al. Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells. J. Physiol. 2008, 586:1307-1319.
87. Leech C.A., et al. Epac2-dependent rap1 activation and the control of islet insulin secretion by glucagon-like peptide-1. Vitam. Horm. 2010, 84:279-302.
88. 2+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in β-cells of phospholipase C-e knockout mice. J. Physiol. 2010, 588:4871-4889.
89. Dzhura I., et al. Phospholipase C-e links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of Langerhans. Islets 2011, 3:121-128.
90. 2+ signal that is essential for insulin secretion in mouse pancreatic islets. Diabetes 2008, 57:868-878.
91. Leech C.A., et al. Facilitation of β-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac. Islets 2010, 2:72-81.
92. 2+ influx. Mol. Pharmacol. 2013, 83:191-205.
93. Kang G., et al. cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells. J. Physiol. 2006, 573:595-609.
94. Kwan E.P., et al. Activation of exchange protein directly activated by cyclic adenosine monophosphate and protein kinase A regulate common and distinct steps in promoting plasma membrane exocytic and granule-to-granule fusions in rat islet beta cells. Pancreas 2007, 35:e45-e54.
95. 2+ sensor in pancreatic beta-cells. Involvement of cAMP-GEFII. Rim2. Piccolo complex in cAMP-dependent exocytosis. J. Biol. Chem. 2002, 277:50497-50502.
96. Shibasaki T., et al. Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:19333-19338.
97. Enserink J.M., et al. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat. Cell Biol. 2002, 4:901-906.
98. Holz G.G., et al. Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors. Cell. Signal. 2008, 20:10-20.
99. Poppe H., et al. Cyclic nucleotide analogs as probes of signaling pathways. Nat. Methods 2008, 5:277-278.
100. Enyeart J.A., Enyeart J.J. Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway. PLoS ONE 2009, 4:e6088.
101. Enyeart J.A., et al. cAMP analogs and their metabolites enhance TREK-1 mRNA and K+ current expression in adrenocortical cells. Mol. Pharmacol. 2010, 77:469-482.
102. 2+ channels, and cortisol synthesis by a cAMP-independent mechanism. Am. J. Physiol. Endocrinol. Metab. 2011, 301:E941-E954.
103. Sand C., et al. 8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic properties. Thromb. Haemost. 2010, 103:662-678.
104. Herfindal L., et al. Off-target effect of the Epac agonist 8-pCPT-2'-O-Me-cAMP on P2Y12 receptors in blood platelets. Biochem. Biophys. Res. Commun. 2013, 437:603-608.
105. Chen H., et al. 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP. Bioorg. Med. Chem. Lett. 2012, 22:4038-4043.
106. Chen H., et al. Identification and characterization of small molecules as potent and specific EPAC2 antagonists. J. Med. Chem. 2013, 56:952-962.
107. Chen H., et al. Efficient synthesis of ESI-09, a novel non-cyclic nucleotide EPAC antagonist. Tetrahedron Lett. 2013, 54:1546-1549.
108. Tsalkova T., et al. Exchange protein directly activated by cAMP isoform 2 is not a direct target of sulfonylurea drugs. Assay Drug Dev. Technol. 2011, 9:88-91.