Skip to main content
SpringerLink
Log in

Role of the cAMP Pathway in Glucose and Lipid Metabolism

  • Chapter
Metabolic Control

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 233))

Abstract

3′–5′-Cyclic adenosine monophosphate (cyclic AMP or cAMP) was first described in 1957 as an intracellular second messenger mediating the effects of glucagon and epinephrine on hepatic glycogenolysis (Berthet et al., J Biol Chem 224(1):463–475, 1957). Since this initial characterization, cAMP has been firmly established as a versatile molecular signal involved in both central and peripheral regulation of energy homeostasis and nutrient partitioning. Many of these effects appear to be mediated at the transcriptional level, in part through the activation of the transcription factor CREB and its coactivators. Here we review current understanding of the mechanisms by which the cAMP signaling pathway triggers metabolic programs in insulin-responsive tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acin-Perez R et al (2009) Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation. Cell Metab 9(3):265–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adler ES et al (2012) Neurochemical characterization and sexual dimorphism of projections from the brain to abdominal and subcutaneous white adipose tissue in the rat. J Neurosci 32(45):15913–15921

    Article  CAS  PubMed  Google Scholar 

  • Ahmad F et al (2009) Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta3-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes. Biochem J 424(3):399–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahn S et al (1998) A dominant-negative inhibitor of CREB reveals that it is a general mediator stimulus-dependent transcription of c-fos. Mol Cell Biol 18:967–977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altarejos JY, Montminy M (2011) CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol 12(3):141–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ammälä C, Ashcroft F, Rorsman P (1993) Calcium-independent potentiation of insulin release by cyclic AMP in single beta-cells. Nature 363(6427):356–358

    Article  PubMed  Google Scholar 

  • Anthonsen MW et al (1998) Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. J Biol Chem 273(1):215–221

    Article  CAS  PubMed  Google Scholar 

  • Arner P et al (1990) Adrenergic regulation of lipolysis in situ at rest and during exercise. J Clin Invest 85(3):893–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arrojo E, Drigo R, Fonseca TL, Werneck-de-Castro JP, Bianco AC (2013) Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling. Biochim Biophys Acta 1830(7):3956–3964

    Article  CAS  Google Scholar 

  • Artner I, Hang Y, Mazur M, Yamamoto T, Guo M, Lindner J, Magnuson MA, Stein R (2010) MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes 59(10):2530–2539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barroso I, Benito B, Garcí-Jiménez C, Hernández A, Obregón MJ, Santisteban P (1999) Norepinephrine, tri-iodothyronine and insulin upregulate glyceraldehyde-3-phosphate dehydrogenase mRNA during Brown adipocyte differentiation. Eur J Endocrinol 141(2):169–179

    Article  CAS  PubMed  Google Scholar 

  • Basit A, Hydrie M, Hakeem R, Ahmedani MY, Masood Q (2004) Frequency of chronic complications of type II diabetes. J Coll Physicians Surg Pak 14:79–83

    PubMed  Google Scholar 

  • Ber I, Shternhall K, Perl S, Ohanuna Z, Goldberg I, Barshack I, Benvenisti-Zarum L, Meivar-Levy I, Ferber S (2003) Functional, persistent, and extended liver to pancreas transdifferentiation. J Biol Chem 278(34):31950–31957

    Article  CAS  PubMed  Google Scholar 

  • Berthet J, Rall TW, Sutherland EW (1957) 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 224(1):463–475

    CAS  PubMed  Google Scholar 

  • Birsoy K, Chen Z, Friedman J (2008) Transcriptional regulation of adipogenesis by KLF4. Cell Metab 7(4):339–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanchet E, Van de Velde S, Matsumura S, Hao E, LeLay J, Kaestner K, Montminy M (2015) Feedback inhibition of CREB signaling promotes beta cell dysfunction in insulin resistance. Cell Rep 10:1149–1157

    Article  CAS  PubMed  Google Scholar 

  • Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR (2005) Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab 90(12):6650–6656

    Article  CAS  PubMed  Google Scholar 

  • Borboni P, Porzio O, Pierucci D, Cicconi S, Magnaterra R, Federici M, Sesti G, Lauro D, D’Agata V, Cavallaro S, Marlier LN (1999) Molecular and functional characterization of pituitary adenylate cyclase-activating polypeptide (PACAP-38)/vasoactive intestinal polypeptide receptors in pancreatic beta-cells and effects of PACAP-38 on components of the insulin secretory system. Endocrinology 140(12):5530–5537

    CAS  PubMed  Google Scholar 

  • Boyda HN et al (2013) Peripheral adrenoceptors: the impetus behind glucose dysregulation and insulin resistance. J Neuroendocrinol 25(3):217–228

    Article  CAS  PubMed  Google Scholar 

  • Brasaemle DL et al (2009) Perilipin A and the control of triacylglycerol metabolism. Mol Cell Biochem 326(1–2):15–21

    Article  CAS  PubMed  Google Scholar 

  • Brown MS, Goldstein J (2008) Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 7:95–96

    Article  CAS  PubMed  Google Scholar 

  • Buck J et al (1999) Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. Proc Natl Acad Sci U S A 96(1):79–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cairns SP, Dulhunty A (1993) Beta-adrenergic potentiation of E-C coupling increases force in rat skeletal muscle. Muscle Nerve 16:1317–1325

    Article  CAS  PubMed  Google Scholar 

  • Cameron IL, Smith RE (1964) Cytological responses of brown fat tissue in cold-exposed rats. J Cell Biol 23:89–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cannon B, Hedin A, Nedergaard J (1982) Exclusive occurrence of thermogenin antigen in brown adipose tissue. FEBS Lett 150(1):129–132

    Article  CAS  PubMed  Google Scholar 

  • Centers for Disease Control and Prevention (2015) Diabetes public health resource. http://www.cdc.gov/diabetes/. Accessed June 2015

  • Chen J et al (1995) A region of adenylyl cyclase 2 critical for regulation by G protein beta gamma subunits. Science 268(5214):1166–1169

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Feng H, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS (2009) G(s)alpha deficiency in skeletal muscle leads to reduced muscle mass, fiber-type switching, and glucose intolerance without insulin resistance or deficiency. Am J Physiol Cell Physiol 296(4):C930–C940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen M et al (2010) G(s)alpha deficiency in adipose tissue leads to a lean phenotype with divergent effects on cold tolerance and diet-induced thermogenesis. Cell Metab 11(4):320–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi YH et al (2006) Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. J Clin Invest 116(12):3240–3251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chrivia JC et al (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365(6449):855–859

    Article  CAS  PubMed  Google Scholar 

  • Clausen T (2003) Na + −K+ pump regulation and skeletal muscle contractility. Physiol Rev 83(4):1269–1324

    Article  CAS  PubMed  Google Scholar 

  • Coppack SW, Jensen M, Miles JM (1994) In vivo regulation of lipolysis in humans. J Lipid Res 35(2):177–193

    CAS  PubMed  Google Scholar 

  • Costes S, Vandewalle B, Tourrel-Cuzin C, Broca C, Linck N, Bertrand G, Kerr-Conte J, Portha B, Pattou F, Bockaert J, Dalle S (2009) Degradation of cAMP-responsive element-binding protein by the ubiquitin-proteasome pathway contributes to glucotoxicity in beta-cells and human pancreatic islets. Diabetes 58:1105–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cummings DE et al (1996) Genetically lean mice result from targeted disruption of the RII beta subunit of protein kinase A. Nature 382(6592):622–626

    Article  CAS  PubMed  Google Scholar 

  • Cypess AM et al (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360(15):1509–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai XQ, Spigelman A, Khan S, Braun M, Manning Fox JE, MacDonald PE (2014) SUMO1 enhances cAMP-dependent exocytosis and glucagon secretion from pancreatic α-cells. J Physiol 592(Pt 17):3715–3726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dalle S, Quoyer J, Varin E, Costes S (2011) Roles and regulation of the transcription factor CREB in pancreatic β-cells. Curr Mol Pharmacol 4:187–195

    Article  CAS  PubMed  Google Scholar 

  • de Jesus LA et al (2001) The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest 108(9):1379–1385

    Article  PubMed  PubMed Central  Google Scholar 

  • de Rooij J et al (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396(6710):474–477

    Article  PubMed  CAS  Google Scholar 

  • Defer N, Best-Belpomme M, Hanoune J (2000) Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase. Am J Physiol Renal Physiol 279(3):F400–F416

    CAS  PubMed  Google Scholar 

  • Dempersmier J, Sambeat A, Gulyaeva O, Paul SM, Hudak CS, Raposo HF, Kwan HY, Kang C, Wong RH, Sul HS (2015) Cold-inducible Zfp516 activates UCP1 transcription to promote browning of white fat and development of brown fat. Mol Cell 57(2):235–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dessauer CW (2009) Adenylyl cyclase--A-kinase anchoring protein complexes: the next dimension in cAMP signaling. Mol Pharmacol 76(5):935–941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Benedetto G et al (2008) Protein kinase A type I and type II define distinct intracellular signaling compartments. Circ Res 103(8):836–844

    Article  PubMed  CAS  Google Scholar 

  • DiFrancesco D, Tortora P (1991) Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature 351(6322):145–147

    Article  CAS  PubMed  Google Scholar 

  • Ding WG, Gromada J (1997) Protein kinase A-dependent stimulation of exocytosis in mouse pancreatic beta-cells by glucose-dependent insulinotropic polypeptide. Diabetes 46(4):615–621

    Article  CAS  PubMed  Google Scholar 

  • Ding WG, Renström E, Rorsman P, Buschard K, Gromada J (1997) Glucagon-like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2 + −induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism. Diabetes 46(5):792–800

    Article  CAS  PubMed  Google Scholar 

  • Dodt C et al (1999) Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans. J Physiol 521(Pt 2):545–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dowse GK, Qin H, Collins VR, Zimmet PZ, Alberti KG, Gareeboo H (1990) Determinants of estimated insulin resistance and beta-cell function in Indian, Creole and Chinese Mauritians. The Mauritius NCD Study Group. Diabetes Res Clin Pract 10:265–279

    Article  CAS  PubMed  Google Scholar 

  • Eberhard CE, Fu A, Reeks C, Screaton RA (2013) CRTC2 is required for β-cell function and proliferation. Endocrinology 154:2308–2317

    Article  CAS  PubMed  Google Scholar 

  • Eckert B, Schwaninger M, Knepel W (1996) Calcium-mobilizing insulin secretagogues stimulate transcription that is directed by the cyclic adenosine 3′,5′-monophosphate/calcium response element in a pancreatic islet beta-cell line. Endocrinology 137:225–233

    CAS  PubMed  Google Scholar 

  • Eckner R et al (1994) Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev 8(8):869–884

    Article  CAS  PubMed  Google Scholar 

  • Ehses JA, Casilla V, Doty T, Pospisilik JA, Winter KD, Demuth HU, Pederson RA, McIntosh CH (2003) Glucose-dependent insulinotropic polypeptide promotes beta-(INS-1) cell survival via cyclic adenosine monophosphate-mediated caspase-3 inhibition and regulation of p38 mitogen-activated protein kinase. Endocrinology 144(10):4433–4445

    Article  CAS  PubMed  Google Scholar 

  • Elliott AD, Ustione A, Piston DW (2015) Somatostatin and insulin mediate glucose-inhibited glucagon secretion in the pancreatic α-cell by lowering cAMP. Am J Physiol Endocrinol Metab 308(2):E130–E143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Maghrabi MR, Claus T, Pilkis J, Pilkis SJ (1982) Regulation of 6-phosphfructo-2-kinase activity by cyclic AMP-dependent phosphorylation. Proc Natl Acad Sci U S A 79:315–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Enerback S et al (1997) Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387(6628):90–94

    Article  CAS  PubMed  Google Scholar 

  • Ezrailson EG, Entman M, Garber AJ (1983) Adrenergic and serotonergic regulation of skeletal muscle metabolism in rat. I. The effects of adrenergic and serotonergic antagonists on the regulation of muscle amino acid release, glycogenolysis, and cyclic nucleotide levels. J Biol Chem 258(20):12494–12498

    CAS  PubMed  Google Scholar 

  • Fedorenko A, Lishko PV, Kirichok Y (2012) Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151(2):400–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fox KE et al (2006) Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. J Biol Chem 281(52):40341–40353

    Article  CAS  PubMed  Google Scholar 

  • Francis SH, Blount MA, Corbin JD (2011) Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev 91(2):651–690

    Article  CAS  PubMed  Google Scholar 

  • Frayn KN (2002) Adipose tissue as a buffer for daily lipid flux. Diabetologia 45(9):1201–1210

    Article  CAS  PubMed  Google Scholar 

  • Froese A et al (2012) Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice. J Clin Invest 122(3):1119–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furman B, Ong W, Pyne NJ (2010) Cyclic AMP signaling in pancreatic islets. Adv Exp Med Biol 654:281–304

    Article  CAS  PubMed  Google Scholar 

  • Gao T, McKenna B, Li C, Reichert M, Nguyen J, Singh T, Yang C, Pannikar A, Doliba N, Zhang T, Stoffers DA, Edlund H, Matschinsky F, Stein R, Stanger BZ (2014) Pdx1 maintains β cell identity and function by repressing an α cell program. Cell Metab 19(2):259–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • George M, Ayuso E, Casellas A, Costa C, Devedjian JC, Bosch F (2002) Beta cell expression of IGF-I leads to recovery from type 1 diabetes. J Clin Invest 109:1153–1163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerhardstein BL, Puri T, Chien AJ, Hosey MM (1999) Identification of the sites phosphorylated by cyclic AMP-dependent protein kinase on the beta 2 subunit of L-type voltage-dependent calcium channels. Biochemistry 38(32):10361–10370

    Article  CAS  PubMed  Google Scholar 

  • Gettys TW et al (1987) Short-term feedback regulation of cAMP by accelerated degradation in rat tissues. J Biol Chem 262(1):333–339

    CAS  PubMed  Google Scholar 

  • Gromada J, Bokvist K, Ding WG, Barg S, Buschard K, Renström E, Rorsman P (1997) Adrenaline stimulates glucagon secretion in pancreatic A-cells by increasing the Ca2+ current and the number of granules close to the L-type Ca2+ channels. J Gen Physiol 110(3):217–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guirguis E, Hockman S, Chung YW, Ahmad F, Gavrilova O, Raghavachari N, Yang Y, Niu G, Chen X, Yu ZX, Liu S, Degerman E, Manganiello V (2013) A role for phosphodiesterase 3B in acquisition of brown fat characteristics by white adipose tissue in male mice. Endocrinology 154(9):3152–3167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gujral UP, Narayan K, Kahn SE, Kanaya AM (2014) The relative associations of β-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: the MASALA study. J Diabetes Complications 28:45–50

    Article  PubMed  Google Scholar 

  • Handa N et al (2008) Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP. J Biol Chem 283(28):19657–19664

    Article  CAS  PubMed  Google Scholar 

  • Hang Y, Stein R (2011) MafA and MafB activity in pancreatic β cells. Trends Endocrinol Metab 22(9):364–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harcourt LJ, Schertzer J, Ryall JG, Lynch GS (2007) Low dose formoterol administration improves muscle function in dystrophic mdx mice without increasing fatigue. Neuromuscul Disord 17:47–55

    Article  PubMed  Google Scholar 

  • Härndahl L, Jing X, Ivarsson R, Degerman E, Ahrén B, Manganiello VC, Renström E, Holst LS (2002) Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta-cell exocytosis and release of insulin. J Biol Chem 277(40):37446–37455

    Article  PubMed  Google Scholar 

  • Hauge-Evans AC, King A, Carmignac D, Richardson CC, Robinson IC, Low MJ, Christie MR, Persaud SJ, Jones PM (2009) Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function. Diabetes 58(2):403–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayes JS, Brunton LL, Mayer SE (1980) Selective activation of particulate cAMP-dependent protein kinase by isoproterenol and prostaglandin E1. J Biol Chem 255(11):5113–5119

    CAS  PubMed  Google Scholar 

  • Heaton GM et al (1978) Brown-adipose-tissue mitochondria: photoaffinity labelling of the regulatory site of energy dissipation. Eur J Biochem 82(2):515–521

    Article  CAS  PubMed  Google Scholar 

  • Heimann E, Jones H, Resjö S, Manganiello VC, Stenson L, Degerman E (2010) Expression and regulation of cyclic nucleotide phosphodiesterases in human and rat pancreatic islets. PLoS One 5(12):e14191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henquin JC, Nenquin M (2014) Activators of PKA and Epac distinctly influence insulin secretion and cytosolic Ca2+ in female mouse islets stimulated by glucose and tolbutamide. Endocrinology 155(9):3274–3287

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Herzig S et al (2001) CREB regulates hepatic gluconeogenesis via the co-activator PGC-1. Nature 413:179–183

    Article  CAS  PubMed  Google Scholar 

  • Hinkle RT, Lefever F, Dolan ET, Reichart DL, Dietrich JA, Gropp KE, Thacker RI, Demuth JP, Stevens PJ, Qu XA, Varbanov AR, Wang F, Isfort RJ (2007) Corticortophin releasing factor 2 receptor agonist treatment significantly slows disease progression in mdx mice. BMC Med 5:18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hollenberg CH, Raben MS, Astwood EB (1961) The lipolytic response to corticotropin. Endocrinology 68:589–598

    Article  CAS  PubMed  Google Scholar 

  • Houslay MD (2010) Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem Sci 35(2):91–100

    Article  CAS  PubMed  Google Scholar 

  • Hui H, Nourparvar A, Zhao X, Perfetti R (2003) Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 144(4):1444–1455

    Article  CAS  PubMed  Google Scholar 

  • Huttunen P, Hirvonen J, Kinnula V (1981) The occurrence of brown adipose tissue in outdoor workers. Eur J Appl Physiol Occup Physiol 46(4):339–345

    Article  CAS  PubMed  Google Scholar 

  • Insel PA (1996) Seminars in medicine of the Beth Israel Hospital, Boston. Adrenergic receptors – evolving concepts and clinical implications. N Engl J Med 334(9):580–585

    Article  CAS  PubMed  Google Scholar 

  • Ishibashi K, Sasaki S, Akiba T, Marumo F (1993) Expression of bone morphogenic protein 7 mRNA in MDCK cells. Biochem Biophys Res Commun 193(1):235–239

    Article  CAS  PubMed  Google Scholar 

  • Ishihara H, Asano T, Tsukuda K, Katagiri H, Inukai K, Anai M, Kikuchi M, Yazaki Y, Miyazaki J, Oka Y (1994) Overexpression of hexokinase I but not GLUT1 glucose transporter alters concentration dependence of glucose-stimulated insulin secretion in pancreatic beta-cell line MIN6. J Biol Chem 269(4):3081–3087

    CAS  PubMed  Google Scholar 

  • Islam D, Zhang N, Wang P, Li H, Brubaker PL, Gaisano HY, Wang Q, Jin T (2009) 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 296(1):E174–E181

    Article  CAS  PubMed  Google Scholar 

  • Iwami G et al (1995) Regulation of adenylyl cyclase by protein kinase A. J Biol Chem 270(21):12481–12484

    Article  CAS  PubMed  Google Scholar 

  • Jambal P, Masterson S, Nesterova A, Bouchard R, Bergman B, Hutton JC, Boxer LM, Reusch JE, Pugazhenthi S (2003) Cytokine-mediated down-regulation of the transcription factor cAMP-response element-binding protein in pancreatic beta-cells. J Biol Chem 278:23055–23065

    Article  CAS  PubMed  Google Scholar 

  • Jhala US, Canettieri G, Screaton RA, Kulkarni RN, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M (2003) cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev 17:1575–1580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19

    Article  CAS  PubMed  Google Scholar 

  • Kai AK, Lam A, Chen Y, Tai AC, Zhang X, Lai AK, Yeung PK, Tam S, Wang J, Lam KS, Vanhoutte PM, Bos JL, Chung SS, Xu A, Chung SK (2013) Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome. FASEB J 27(10):4122–4135

    Article  CAS  PubMed  Google Scholar 

  • Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM (2009) Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 460(7259):1154–1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamenetsky M et al (2006) Molecular details of cAMP generation in mammalian cells: a tale of two systems. J Mol Biol 362(4):623–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaneto H, Miyatsuka T, Kawamori D, Yamamoto K, Kato K, Shiraiwa T, Katakami N, Yamasaki Y, Matsuhisa M, Matsuoka TA (2008) PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function. Endocr J 55(2):235–252

    Article  CAS  PubMed  Google Scholar 

  • Kang G, Chepurny O, Malester B, Rindler MJ, Rehmann H, Bos JL, Schwede F, Coetzee WA, Holz GG (2006) cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells. J Physiol 573(Pt 3):595–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kashima Y, Miki T, Shibasaki T, Ozaki N, Miyazaki M, Yano H, Seino S (2001) Critical role of cAMP-GEFII––Rim2 complex in incretin-potentiated insulin secretion. J Biol Chem 276:46046–46053

    Article  CAS  PubMed  Google Scholar 

  • Keravis T, Lugnier C (2010) Cyclic nucleotide phosphodiesterases (PDE) and peptide motifs. Curr Pharm Des 16(9):1114–1125

    Article  CAS  PubMed  Google Scholar 

  • Kim MJ, Kang J, Park YG, Ryu GR, Ko SH, Jeong IK, Koh KH, Rhie DJ, Yoon SH, Hahn SJ, Kim MS, Jo YH (2006) Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element. J Endocrinol 188(3):623–633

    Article  CAS  PubMed  Google Scholar 

  • Kim SJ, Nian C, Widenmaier S, McIntosh CH (2008) Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response element binding protein (CREB) and cAMP-responsive CREB coactivator 2. Mol Cell Biol 28(5):1644–1656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimple ME, Keller M, Rabaglia MR, Pasker RL, Neuman JC, Truchan NA, Brar HK, Attie AD (2013) Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion. Diabetes 62(6):1904–1912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kolditz CI, Langin D (2010) Adipose tissue lipolysis. Curr Opin Clin Nutr Metab Care 13(4):377–381

    Article  CAS  PubMed  Google Scholar 

  • Kong X, Banks A, Liu T, Kazak L, Rao RR, Cohen P, Wang X, Yu S, Lo JC, Tseng YH, Cypess AM, Xue R, Kleiner S, Kang S, Spiegelman BM, Rosen ED (2014) IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 158(1):69–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S, Hedrick S, Xu W, Boussouar F, Brindle P, Takemori H, Montminy M (2005) The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 437(7062):1109–1111

    Article  CAS  PubMed  Google Scholar 

  • Leiser M, Fleischer N (1996) cAMP-dependent phosphorylation of the cardiac-type alpha 1 subunit of the voltage-dependent Ca2+ channel in a murine pancreatic beta-cell line. Diabetes 45(10):1412–1418

    Article  CAS  PubMed  Google Scholar 

  • Lidell ME et al (2013) Evidence for two types of brown adipose tissue in humans. Nat Med 19(5):631–634

    Article  CAS  PubMed  Google Scholar 

  • Light PE, Manning Fox J, Riedel MJ, Wheeler MB (2002) Glucagon-like peptide-1 inhibits pancreatic ATP-sensitive potassium channels via a protein kinase A- and ADP-dependent mechanism. Mol Endocrinol 16(9):2135–2144

    Article  CAS  PubMed  Google Scholar 

  • Lin B, Morris D, Chou JY (1997) The role of HNF1alpha, HNF3gamma, and cyclic AMP in glucose-6-phosphatase gene activation. Biochemistry 36(46):14096–14106

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J 3rd, Olefsky J, Guarente L, Montminy M (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456(7219):269–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Love JA, Richards N, Owyang C, Dawson DC (1998) Muscarinic modulation of voltage-dependent Ca2+ channels in insulin-secreting HIT-T15 cells. Am J Physiol 274(2 Pt 1):G397–G405

    CAS  PubMed  Google Scholar 

  • Maltin CA, Hay S, Delday MI, Lobley GE, Reeds PJ (1989) The action of the beta-agonist clenbuterol on protein metabolism in innervated and denervated phasic muscles. Biochem J 261:965–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mattsson CL, Csikasz R, Chernogubova E, Yamamoto DL, Hogberg HT, Amri EZ, Hutchinson DS, Bengtsson T (2011) β1-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β3-adrenergic receptor-knockout mice via nonshivering thermogenesis. Am J Physiol Endocrinol Metab 301(6):E1108–E1118

    Article  CAS  PubMed  Google Scholar 

  • McKinnon CM, Docherty K (2001) Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function. Diabetologia 44(10):1203–1214

    Article  CAS  PubMed  Google Scholar 

  • Metz SA (1988) Epinephrine impairs insulin release by a mechanism distal to calcium mobilization. Similarity to lipoxygenase inhibitors. Diabetes 37(1):65–73

    Article  CAS  PubMed  Google Scholar 

  • Monroe MB et al (2001) Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans. Am J Physiol Endocrinol Metab 280(5):E740–E744

    CAS  PubMed  Google Scholar 

  • Morgan DG, Kulkarni R, Hurley JD, Wang ZL, Wang RM, Ghatei MA, Karlsen AE, Bloom SR, Smith DM (1998) Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells. Diabetologia 41(12):1482–1491

    Article  CAS  PubMed  Google Scholar 

  • Mullur R, Liu Y, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94(2):355–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murakami T, Nishiyama T, Shirotani T, Shinohara Y, Kan M, Ishii K, Kanai F, Nakazuru S, Ebina Y (1992) Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes. J Biol Chem 267:9300–9306

    CAS  PubMed  Google Scholar 

  • Niehof M, Manns MP, Trautwein C (1997) CREB controls LAP/C/EBP beta transcription. Mol Cell Biol 17(7):3600–3613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishizawa Y, Bray GA (1978) Ventromedial hypothalamic lesions and the mobilization of fatty acids. J Clin Invest 61(3):714–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niwa T, Matsukawa Y, Senda T, Nimura Y, Hidaka H, Niki I (1998) Acetylcholine activates intracellular movement of insulin granules in pancreatic beta-cells via inositol trisphosphate-dependent [correction of triphosphate-dependent] mobilization of intracellular Ca2+. Diabetes 47(11):1699–1706

    Article  CAS  PubMed  Google Scholar 

  • Offield MF, Jetton T, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV (1996) PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 122(3):983–995

    CAS  PubMed  Google Scholar 

  • Okla M, Ha J, Temel RE, Chung S (2015) BMP7 drives human adipogenic stem cells into metabolically active beige adipocytes. Lipids 50(2):111–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olefsky JM (1977) Insensitivity of large rat adipocytes to the antilipolytic effects of insulin. J Lipid Res 18(4):459–464

    CAS  PubMed  Google Scholar 

  • Pagnon J et al (2012) Identification and functional characterization of protein kinase A phosphorylation sites in the major lipolytic protein, adipose triglyceride lipase. Endocrinology 153(9):4278–4289

    Article  CAS  PubMed  Google Scholar 

  • Park BO, Ahrends R, Teruel MN (2012) Consecutive positive feedback loops create a bistable switch that controls preadipocyte-to-adipocyte conversion. Cell Rep 2(4):976–990

    Article  CAS  PubMed  Google Scholar 

  • Perfetti R, Zhou J, Doyle ME, Egan JM (2000) Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 141(12):4600–4605

    Article  CAS  PubMed  Google Scholar 

  • Petersen RK et al (2008) Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Mol Cell Biol 28(11):3804–3816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poitout V, Robertson R (2008) Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 29:351–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Puddu A, Sanguineti R, Montecucco F, Viviani GL (2015) Effects of high glucose levels and glycated serum on GIP responsiveness in the pancreatic beta cell line HIT-T15. J Diabetes Res 2015:326359

    Article  PubMed  PubMed Central  Google Scholar 

  • Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92(6):829–839

    Article  CAS  PubMed  Google Scholar 

  • Purwana I, Zheng J, Li X, Deurloo M, Son DO, Zhang Z, Liang C, Shen E, Tadkase A, Feng ZP, Li Y, Hasilo C, Paraskevas S, Bortell R, Greiner DL, Atkinson M, Prud’homme GJ, Wang Q (2014) GABA promotes human β-cell proliferation and modulates glucose homeostasis. Diabetes 63:4197–4205

    Article  CAS  PubMed  Google Scholar 

  • Quinn PG, Granner DK (1990) Cyclic AMP-dependent protein kinase regulates transcription of the phosphoenolpyruvate carboxykinase gene but not binding of nuclear factors to the cyclic AMP regulatory element. Mol Cell Biol 10:3357–3364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richards CS, Yokoyama M, Furuya E, Uyeda K (1982) Reciprocal changes in fructose-2,6-bisphosphate, 2-kinase and fructose-2,6-bisphosphatase activity in response to glucagon and epinephrine. Biochem Biophys Res Commun 104:1073–1079

    Article  CAS  PubMed  Google Scholar 

  • Richelsen B, Pedersen O (1985) Beta-adrenergic regulation of prostaglandin E2 receptors in human and rat adipocytes. Endocrinology 116(3):1182–1188

    Article  CAS  PubMed  Google Scholar 

  • Rim JS, Kozak L (2002) Regulatory motifs for CREB-binding protein and Nfe2l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene. J Biol Chem 277(37):34589–34600

    Article  CAS  PubMed  Google Scholar 

  • Rosen ED, Spiegelman BM (2014) What we talk about when we talk about fat. Cell 156(1–2):20–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russell TR, Ho R (1976) Conversion of 3T3 fibroblasts into adipose cells: triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl xanthine. Proc Natl Acad Sci U S A 73(12):4516–4520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryall JG, Schertzer J, Alabakis TM, Gehrig SM, Plant DR, Lynch GS (2008) Intramuscular beta2-agonist administration enhances early regeneration and functional repair in rat skeletal muscle after myotoxic injury. J Appl Physiol 105:165–172

    Article  CAS  PubMed  Google Scholar 

  • Saida K, Van Breemen C (1984) Cyclic AMP modulation of adrenoreceptor-mediated arterial smooth muscle contraction. J Gen Physiol 84(2):307–318

    Article  CAS  PubMed  Google Scholar 

  • Screaton RA, Conkright M, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR 3rd, Takemori H, Okamoto M, Montminy M (2004) The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119:61–74

    Article  CAS  PubMed  Google Scholar 

  • Sculptoreanu A, Scheuer T, Catterall WA (1993) Voltage-dependent potentiation of L-type Ca2+ channels due to phosphorylation by cAMP-dependent protein kinase. Nature 364(6434):240–243

    Article  CAS  PubMed  Google Scholar 

  • Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6(1):38–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seematter G et al (2004) Relationship between stress, inflammation and metabolism. Curr Opin Clin Nutr Metab Care 7(2):169–173

    Article  CAS  PubMed  Google Scholar 

  • Semple RK, Crowley V, Sewter CP, Laudes M, Christodoulides C, Considine RV, Vidal-Puig A, O’Rahilly S (2004) Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjects. Int J Obes Relat Metab Disord 28(1):176–179

    Article  CAS  PubMed  Google Scholar 

  • Sette C, Iona S, Conti M (1994) The short-term activation of a rolipram-sensitive, cAMP-specific phosphodiesterase by thyroid-stimulating hormone in thyroid FRTL-5 cells is mediated by a cAMP-dependent phosphorylation. J Biol Chem 269(12):9245–9252

    CAS  PubMed  Google Scholar 

  • Shimizu Y, Satoh S, Yano H, Minokoshi Y, Cushman SW, Shimazu T (1998) Effects of noradrenaline on the cell-surface glucose transporters in cultured brown adipocytes: novel mechanism for selective activation of GLUT1 glucose transporters. Biochem J 330(Pt 1):397–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siersbaek R et al (2014) Molecular architecture of transcription factor hotspots in early adipogenesis. Cell Rep 7(5):1434–1442

    Article  CAS  PubMed  Google Scholar 

  • Silva JE (2006) Thermogenic mechanisms and their hormonal regulation. Physiol Rev 86(2):435–464

    Article  CAS  PubMed  Google Scholar 

  • Silva JE, Larsen PR (1983) Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature 305(5936):712–713

    Article  CAS  PubMed  Google Scholar 

  • Sinnarajah S et al (2001) RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III. Nature 409(6823):1051–1055

    Article  CAS  PubMed  Google Scholar 

  • Skala JP, Knight BL (1977) Protein kinases in brown adipose tissue of developing rats. State of activation of protein kinase during development and cold exposure and its relationship to adenosine 3′:5′-monophosphate, lipolysis, and heat production. J Biol Chem 252(3):1064–1070

    CAS  PubMed  Google Scholar 

  • Smith FD et al (2013) Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation. Elife 2:e01319

    PubMed  PubMed Central  Google Scholar 

  • Soderling TR, Hickenbottom J, Reimann EM, Hunkeler FL, Walsh DA, Krebs EG (1970) Inactivation of glycogen synthetase and activation of phosphorylase kinase by muscle adenosine 3′,5′-monophosphate-dependent protein kinases. J Biol Chem 245:6317–6328

    CAS  PubMed  Google Scholar 

  • Song WJ, Schreiber W, Zhong E, Liu FF, Kornfeld BD, Wondisford FE, Hussain MA (2008) Exendin-4 stimulation of cyclin A2 in beta-cell proliferation. Diabetes 57(9):2371–2381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Staimez LR, Weber M, Ranjani H, Ali MK, Echouffo-Tcheugui JB, Phillips LS, Mohan V, Narayan KM (2013) Evidence of reduced β-cell function in Asian Indians with mild dysglycemia. Diabetes Care 36:2772–2778

    Article  PubMed  PubMed Central  Google Scholar 

  • Studer RK, Borle AB (1982) Differences between male and female rats in the regulation of hepatic glycogenolysis. The relative role of calcium and cAMP in phosphorylase activation by catecholamines. J Biol Chem 257(14):7987–7993

    CAS  PubMed  Google Scholar 

  • Studer RK, Snowdowne KW, Borle AB (1984) Regulation of hepatic glycogenolysis by glucagon in male and female rats. Role of cAMP and Ca2+ and interactions between epinephrine and glucagon. J Biol Chem 259(6):3596–3604

    CAS  PubMed  Google Scholar 

  • Sun X, Dang F, Zhang D, Yuan Y, Zhang C, Wu Y, Wang Y, Liu Y (2015) Glucagon-CREB/CRTC2 signaling cascade regulates hepatic BMAL1 protein. J Biol Chem 290(4):2189–2197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang QQ, Lane MD (2012) Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem 81:715–736

    Article  CAS  PubMed  Google Scholar 

  • Thomas SA, Palmiter RD (1997) Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387(6628):94–97

    Article  CAS  PubMed  Google Scholar 

  • Thorens B, Guillam M, Beermann F, Burcelin R, Jaquet M (2000) Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion. J Biol Chem 275(31):23751–23758

    Article  CAS  PubMed  Google Scholar 

  • Tourrel C, Bailbé D, Meile MJ, Kergoat M, Portha B (2001) Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 50:1562–1570

    Article  CAS  PubMed  Google Scholar 

  • Valverde I et al (1979) Calmodulin activation of adenylate cyclase in pancreatic islets. Science 206(4415):225–227

    Article  CAS  PubMed  Google Scholar 

  • van Marken Lichtenbelt WD et al (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360(15):1500–1508

    Article  PubMed  Google Scholar 

  • Virtanen KA et al (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360(15):1518–1525

    Article  CAS  PubMed  Google Scholar 

  • Walsh DA, Perkins JP, Krebs EG (1968) An adenosine 3′,5′-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem 243(13):3763–3765

    CAS  PubMed  Google Scholar 

  • Wang Y, Perfetti R, Greig NH, Holloway HW, DeOre KA, Montrose-Rafizadeh C, Elahi D, Egan JM (1997) Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats. J Clin Invest 99:2883–2889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Iezzi M, Theander S, Antinozzi PA, Gauthier BR, Halban PA, Wollheim CB (2005) Suppression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP-1 signalling in INS-1 cells. Diabetologia 48(4):720–731

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Inoue H, Ravnskjaer K, Viste K, Miller N, Liu Y, Hedrick S, Vera L, Montminy M (2010) Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity. Proc Natl Acad Sci U S A 107(7):3087–3092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Welters HJ, Diakogiannaki E, Mordue JM, Tadayyon M, Smith SA, Morgan NG (2006) Differential protective effects of palmitoleic acid and cAMP on caspase activation and cell viability in pancreatic beta-cells exposed to palmitate. Apoptosis 11(7):1231–1238

    Article  CAS  PubMed  Google Scholar 

  • White JE, Engel FL (1958) Lipolytic action of corticotropin on rat adipose tissue in vitro. J Clin Invest 37(11):1556–1563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vázquez MJ, Morgan D, Csikasz RI, Gallego R, Rodriguez-Cuenca S, Dale M, Virtue S, Villarroya F, Cannon B, Rahmouni K, López M, Vidal-Puig A (2012) BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 149(4):871–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Withers DJ, Burks D, Towery HH, Altamuro SL, Flint CL, White MF (1999) Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Nat Genet 23:32–40

    CAS  PubMed  Google Scholar 

  • Wynshaw-Boris A, Short J, Loose DS, Hanson RW (1986) Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. I. Multiple hormone regulatory elements and the effects of enhancers. J Biol Chem 261:9714–9720

    CAS  PubMed  Google Scholar 

  • Yabe D, Seino Y (2011) Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and β cell preservation. Prog Biophys Mol Biol 107(2):248–256

    Article  CAS  PubMed  Google Scholar 

  • Yasuda K et al (2006) Adrenergic receptor polymorphisms and autonomic nervous system function in human obesity. Trends Endocrinol Metab 17(7):269–275

    Article  CAS  PubMed  Google Scholar 

  • Yokomori N, Tawata M, Hosaka Y, Onaya T (1992) Transcriptional regulation of hexokinase I mRNA levels by TSH in cultured rat thyroid FRTL5 cells. Life Sci 51(20):1613–1619

    Article  CAS  PubMed  Google Scholar 

  • Yoshimasa T et al (1987) Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation. Nature 327(6117):67–70

    Article  CAS  PubMed  Google Scholar 

  • Yosida M, Dezaki K, Uchida K, Kodera S, Lam NV, Ito K, Rita RS, Yamada H, Shimomura K, Ishikawa SE, Sugawara H, Kawakami M, Tominaga M, Yada T, Kakei M (2014) Involvement of cAMP/EPAC/TRPM2 activation in glucose- and incretin-induced insulin secretion. Diabetes 63(10):3394–3403

    Article  CAS  PubMed  Google Scholar 

  • Zaccolo M (2011) Spatial control of cAMP signalling in health and disease. Curr Opin Pharmacol 11(6):649–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaccolo M, Pozzan T (2002) Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes. Science 295(5560):1711–1715

    Article  CAS  PubMed  Google Scholar 

  • Zhang JW et al (2004) Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta gene during adipogenesis. J Biol Chem 279(6):4471–4478

    Article  CAS  PubMed  Google Scholar 

  • Zhang EE, Liu Y, Dentin R, Pongsawakul PY, Liu AC, Hirota T, Nusinow DA, Sun X, Landais S, Kodama Y, Brenner DA, Montminy M, Kay SA (2010) Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med 16(10):1152–1156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao AZ, Zhao H, Teague J, Fujimoto W, Beavo JA (1997) Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B. Proc Natl Acad Sci U S A 94(7):3223–3228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou J, Pineyro M, Wang X, Doyle ME, Egan JM (2002) Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. J Cell Physiol 192(3):304–314

    Article  CAS  PubMed  Google Scholar 

  • Ziegler MG et al (2012) Epinephrine and the metabolic syndrome. Curr Hypertens Rep 14(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Zippin JH et al (2004) Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain. J Cell Biol 164(4):527–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Salk Institute, La Jolla, CA, 92037, USA

    Kim Ravnskjaer, Anila Madiraju & Marc Montminy

Authors
  1. Kim Ravnskjaer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anila Madiraju
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marc Montminy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc Montminy .

Editor information

Editors and Affiliations

  1. Helmholtz Center Munich, and Heidelberg University Hospital, Professor and Director, Institute for Diabetes and Cancer IDC, and Joint Heidelberg-IDC Translational Diabetes Program, Neuherberg, Germany

    Stephan Herzig

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ravnskjaer, K., Madiraju, A., Montminy, M. (2015). Role of the cAMP Pathway in Glucose and Lipid Metabolism. In: Herzig, S. (eds) Metabolic Control. Handbook of Experimental Pharmacology, vol 233. Springer, Cham. https://doi.org/10.1007/164_2015_32

Download citation

Publish with us

Policies and ethics

Search

Navigation