KEGG   PATHWAY: aamp04922
Entry
aamp04922                   Pathway                                
Name
Glucagon signaling pathway - Arvicola amphibius (Eurasian water vole)
Description
Glucagon is conventionally regarded as a counterregulatory hormone for insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Glucagon also stimulates hepatic mitochondrial beta-oxidation to supply energy for glucose production. Glucagon performs its main effect via activation of adenylate cyclase. The adenylate-cyclase-derived cAMP activates protein kinase A (PKA), which then phosphorylates downstream targets, such as cAMP response element binding protein (CREB) and the bifunctional enzyme 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase (one of the isoforms being PFK/FBPase 1, encoded by PFKFB1).
Class
Organismal Systems; Endocrine system
Pathway map
aamp04922  Glucagon signaling pathway
aamp04922

Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119818643  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119820487  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119827246  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119807439  Pde3b; LOW QUALITY PROTEIN: cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
119819991  Gcg; pro-glucagon [KO:K05259]
119813133  Gcgr; glucagon receptor isoform X1 [KO:K04583]
119814107  Gnas; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
119814944  neuroendocrine secretory protein 55 isoform X1 [KO:K04632]
119809754  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
119800975  Prkacb; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
119802004  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119820446  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
119819075  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
119822546  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
119814789  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
119821362  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
119801303  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
119826298  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
119806715  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
119807891  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
119809647  Ppp4r3b; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
119804542  protein PPP4R3C-like [KO:K17491]
119818489  Ppp4r3a; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
119813379  Ppp4c; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
119801276  Crtc2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
119810131  Sik2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
119822927  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
119811558  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
119809862  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
119823319  Sik1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
119812597  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
119814344  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
119814366  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
119814933  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
119824882  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
119806390  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
119806213  Itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
119823109  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
119800939  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
119800012  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
119800123  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
119823004  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
119826596  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
119800462  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
119800784  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
119808786  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
119814221  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
119826452  Foxo1; forkhead box protein O1 [KO:K07201]
119822232  Sirt1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
119822872  Ppara; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
119802993  Prmt1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
119819699  G6pc2; LOW QUALITY PROTEIN: glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
119812167  G6pc1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
119812873  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
119814634  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
119800022  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
119819005  Cpt1a; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
119822804  Cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
119802933  Cpt1c; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
119808488  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
119802804  Gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
119801764  Phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
119804574  Phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
119804692  Phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
119825273  Phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
119807018  Phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
119821021  Calm3; calmodulin-3 [KO:K02183]
119808332  Calm2; calmodulin-2 [KO:K02183]
119808754  Calml4; calmodulin-like protein 4 [KO:K02183]
119809106  calmodulin-1 [KO:K02183]
119815477  calmodulin-1 [KO:K02183]
119817551  Calml3; calmodulin-like protein 3 [KO:K02183]
119817552  calmodulin-4-like [KO:K02183]
119818370  Calm1; calmodulin-1 [KO:K02183]
119814546  Pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
119814614  Pygm; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
119818423  Pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
119804606  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
119816370  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
119810200  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
119801352  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
119825157  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
119820999  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
119822790  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
119806497  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
119811154  Acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119824641  Acacb; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119816753  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
119826881  Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
119820164  Gck; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
119817030  Fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
119817693  Fbp1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
119822448  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
119822796  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
119816493  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
119827916  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
119822577  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
119816391  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
119816427  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
119823112  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
119810483  Pkm; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
119827726  pyruvate kinase PKM-like isoform X1 [KO:K00873] [EC:2.7.1.40]
119823978  pyruvate kinase PKM [KO:K00873] [EC:2.7.1.40]
119801461  Pdha2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
119804661  Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
119827042  Pdhb; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
119821331  Ldhal6b; L-lactate dehydrogenase A-like 6B isoform X1 [KO:K00016] [EC:1.1.1.27]
121677285  LOW QUALITY PROTEIN: L-lactate dehydrogenase C chain-like [KO:K00016] [EC:1.1.1.27]
119802672  L-lactate dehydrogenase C chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
119802859  Ldha; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
119807001  Ldhb; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
Compound
C00022  Pyruvate
C00024  Acetyl-CoA
C00026  2-Oxoglutarate
C00031  D-Glucose
C00036  Oxaloacetate
C00040  Acyl-CoA
C00042  Succinate
C00074  Phosphoenolpyruvate
C00076  Calcium cation
C00083  Malonyl-CoA
C00085  D-Fructose 6-phosphate
C00103  D-Glucose 1-phosphate
C00122  Fumarate
C00149  (S)-Malate
C00158  Citrate
C00182  Glycogen
C00186  (S)-Lactate
C00197  3-Phospho-D-glycerate
C00311  Isocitrate
C00354  D-Fructose 1,6-bisphosphate
C00575  3',5'-Cyclic AMP
C00631  2-Phospho-D-glycerate
C00665  beta-D-Fructose 2,6-bisphosphate
C00668  alpha-D-Glucose 6-phosphate
C01172  beta-D-Glucose 6-phosphate
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:12626323
  Authors
Jiang G, Zhang BB
  Title
Glucagon and regulation of glucose metabolism.
  Journal
Am J Physiol Endocrinol Metab 284:E671-8 (2003)
DOI:10.1152/ajpendo.00492.2002
Reference
PMID:24692138
  Authors
Rui L
  Title
Energy metabolism in the liver.
  Journal
Compr Physiol 4:177-97 (2014)
DOI:10.1002/cphy.c130024
Reference
PMID:22004992
  Authors
Jitrapakdee S
  Title
Transcription factors and coactivators controlling nutrient and hormonal regulation of hepatic gluconeogenesis.
  Journal
Int J Biochem Cell Biol 44:33-45 (2012)
DOI:10.1016/j.biocel.2011.10.001
Reference
PMID:16601267
  Authors
Desvergne B, Michalik L, Wahli W.
  Title
Transcriptional regulation of metabolism.
  Journal
Physiol Rev 86:465-514 (2006)
DOI:10.1152/physrev.00025.2005
Reference
PMID:22550228
  Authors
Hardie DG
  Title
Organismal carbohydrate and lipid homeostasis.
  Journal
Cold Spring Harb Perspect Biol 4:a006031 (2012)
DOI:10.1101/cshperspect.a006031
Reference
PMID:22796337
  Authors
Hasenour CM, Berglund ED, Wasserman DH
  Title
Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver.
  Journal
Mol Cell Endocrinol 366:152-62 (2013)
DOI:10.1016/j.mce.2012.06.018
Reference
PMID:18669612
  Authors
Quesada I, Tuduri E, Ripoll C, Nadal A
  Title
Physiology of the pancreatic alpha-cell and glucagon secretion: role in glucose homeostasis and diabetes.
  Journal
J Endocrinol 199:5-19 (2008)
DOI:10.1677/JOE-08-0290
Reference
PMID:24238363
  Authors
Oh KJ, Han HS, Kim MJ, Koo SH
  Title
CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis.
  Journal
BMB Rep 46:567-74 (2013)
DOI:10.5483/BMBRep.2013.46.12.248
Reference
PMID:16479585
  Authors
Cheng A, Saltiel AR
  Title
More TORC for the gluconeogenic engine.
  Journal
Bioessays 28:231-4 (2006)
DOI:10.1002/bies.20375
Reference
PMID:21346730
  Authors
Altarejos JY, Montminy M
  Title
CREB and the CRTC co-activators: sensors for hormonal and metabolic signals.
  Journal
Nat Rev Mol Cell Biol 12:141-51 (2011)
DOI:10.1038/nrm3072
Reference
PMID:24393785
  Authors
Pernicova I, Korbonits M
  Title
Metformin--mode of action and clinical implications for diabetes and cancer.
  Journal
Nat Rev Endocrinol 10:143-56 (2014)
DOI:10.1038/nrendo.2013.256
Reference
PMID:20735177
  Authors
Hirota K, Fukamizu A
  Title
Transcriptional regulation of energy metabolism in the liver.
  Journal
J Recept Signal Transduct Res 30:403-9 (2010)
DOI:10.3109/10799893.2010.509730
Reference
PMID:21941300
  Authors
Chalkiadaki A, Guarente L
  Title
Metabolic signals regulate SIRT1 expression.
  Journal
EMBO Rep 12:985-6 (2011)
DOI:10.1038/embor.2011.179
Reference
PMID:22249520
  Authors
Chalkiadaki A, Guarente L
  Title
Sirtuins mediate mammalian metabolic responses to nutrient availability.
  Journal
Nat Rev Endocrinol 8:287-96 (2012)
DOI:10.1038/nrendo.2011.225
Reference
PMID:19912989
  Authors
Tang BL, Chua CE
  Title
Is systemic activation of Sirt1 beneficial for ageing-associated metabolic disorders?
  Journal
Biochem Biophys Res Commun 391:6-10 (2010)
DOI:10.1016/j.bbrc.2009.11.016
Reference
PMID:22503562
  Authors
Ozcan L, Wong CC, Li G, Xu T, Pajvani U, Park SK, Wronska A, Chen BX, Marks AR, Fukamizu A, Backs J, Singer HA, Yates JR 3rd, Accili D, Tabas I
  Title
Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.
  Journal
Cell Metab 15:739-51 (2012)
DOI:10.1016/j.cmet.2012.03.002
Reference
PMID:22495310
  Authors
Wang Y, Li G, Goode J, Paz JC, Ouyang K, Screaton R, Fischer WH, Chen J, Tabas I, Montminy M
  Title
Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes.
  Journal
Nature 485:128-32 (2012)
DOI:10.1038/nature10988
Related
pathway
aamp00010  Glycolysis / Gluconeogenesis
aamp00020  Citrate cycle (TCA cycle)
aamp00061  Fatty acid biosynthesis
aamp00190  Oxidative phosphorylation
aamp04020  Calcium signaling pathway
aamp04024  cAMP signaling pathway
aamp04068  FoxO signaling pathway
aamp04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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