KEGG   PATHWAY: npo04922
Entry
npo04922                    Pathway                                
Name
Glucagon signaling pathway - Nyctereutes procyonoides (raccoon dog)
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
npo04922  Glucagon signaling pathway
npo04922

Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129508823  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129495892  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129499851  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129517633  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129514778  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129505013  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
129498394  GCG; pro-glucagon [KO:K05259]
129511187  GCGR; glucagon receptor [KO:K04583]
129497792  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
129497848  neuroendocrine secretory protein 55 [KO:K04632]
129512833  guanine nucleotide-binding protein G(s) subunit alpha-like isoform X1 [KO:K04632]
129498939  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
129519960  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129521768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
129522997  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129518269  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
129498595  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
129511576  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129508719  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
129494799  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129503105  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129515926  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129522278  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129502771  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
129496034  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
129517847  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
129511410  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
129520146  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
129509089  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
129497381  SIK2; serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
129511409  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
129520280  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
129510471  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
129502136  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
129500644  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129496894  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
129504276  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
129497646  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129500550  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
129521608  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
129505465  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
129512495  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
129523448  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
129509604  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
129521210  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
129495049  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
129511439  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
129515997  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129509461  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129509507  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129521159  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129504466  FOXO1; forkhead box protein O1 [KO:K07201]
129509439  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
129511914  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
129499931  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
129493800  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
129504283  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
129498322  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
129498386  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
129499544  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
129499947  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
129511812  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
129500968  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
129505699  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
129499835  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
129517677  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
129517708  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
129513401  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
129519538  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
129519557  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
129495972  CALM1; calmodulin-1 [KO:K02183]
129497741  CALML6; calmodulin-like protein 6 [KO:K02183]
129506414  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
129500769  CALM3; calmodulin-3 [KO:K02183]
129511712  CALM2; calmodulin-2 isoform X1 [KO:K02183]
129513685  calmodulin-like protein 3 [KO:K02183]
129513765  CALML5; calmodulin-like protein 5 [KO:K02183]
129495996  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
129506891  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
129500170  PYGM; LOW QUALITY PROTEIN: glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
129517818  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
129497187  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
129509489  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
129508196  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
129501380  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
129515690  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
129523044  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
129517320  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
129507974  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
129507647  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
129520456  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
129498925  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
129515614  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
129499641  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
129500632  FBP1; fructose-1,6-bisphosphatase 1 isoform X1 [KO:K03841] [EC:3.1.3.11]
129502146  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
129498336  LOW QUALITY PROTEIN: ATP-dependent 6-phosphofructokinase, muscle type-like [KO:K00850] [EC:2.7.1.11]
129505662  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
129513628  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
129515966  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
129523329  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
129506262  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
129512623  pyruvate kinase PKM-like [KO:K00873] [EC:2.7.1.40]
129501948  PDHA2; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
129517649  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
129522554  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
129509271  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
129495708  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
129495714  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
129503422  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
129497391  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
129504967  L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
129505078  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
129505360  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
129505617  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
129506650  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
129500253  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
129507858  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
129516171  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
129516545  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
129516565  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
129516568  L-lactate dehydrogenase A chain-like isoform X1 [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
npo00010  Glycolysis / Gluconeogenesis
npo00020  Citrate cycle (TCA cycle)
npo00061  Fatty acid biosynthesis
npo00190  Oxidative phosphorylation
npo04020  Calcium signaling pathway
npo04024  cAMP signaling pathway
npo04068  FoxO signaling pathway
npo04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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