KEGG   PATHWAY: nasi04922
Entry
nasi04922                   Pathway                                
Name
Glucagon signaling pathway - Neophocaena asiaeorientalis asiaeorientalis (Yangtze finless porpoise)
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
nasi04922  Glucagon signaling pathway
nasi04922

Organism
Neophocaena asiaeorientalis asiaeorientalis (Yangtze finless porpoise) [GN:nasi]
Gene
112405757  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112408453  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112415459  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112407641  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
112393625  GCG; glucagon isoform X1 [KO:K05259]
112410385  GCGR; glucagon receptor [KO:K04583]
112402955  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
112402987  neuroendocrine secretory protein 55-like [KO:K04632]
112404518  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112414741  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
112415075  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112395221  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
112391502  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
112394733  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112402296  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
112397455  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
112411704  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
112400124  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
112401787  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
112406282  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
112404818  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
112393862  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
112399345  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
112401723  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
112405713  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
112409521  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
112394621  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
112400037  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
112408660  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
112395611  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
112402291  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
112412530  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
112412538  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
112391181  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
112400978  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
112391770  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
112414026  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112396846  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112393713  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
112401437  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112392624  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
112396793  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
112400110  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
112401050  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
112391103  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
112406687  FOXO1; forkhead box protein O1 [KO:K07201]
112413531  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
112394582  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
112415635  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
112410110  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
112400500  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
112407380  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
112403085  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
112405031  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
112402414  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
112394647  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
112415460  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
112415516  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
112391784  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
112395916  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
112396983  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
112391609  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
112399190  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
112399241  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
112409928  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
112410874  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
112405194  CALM2; calmodulin-2 [KO:K02183]
112393864  CALM1; calmodulin-1 [KO:K02183]
112407558  calmodulin-like [KO:K02183]
112407559  calmodulin-like protein 3 [KO:K02183]
112400993  calmodulin-like [KO:K02183]
112415452  CALM3; calmodulin-3 [KO:K02183]
112402391  PYGM; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
112404645  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
112392859  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
112414611  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
112405979  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
112407082  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
112412979  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
112408820  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
112411852  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
112405875  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
112394236  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
112408086  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
112397285  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
112399527  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
112392358  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
112401344  GCK; glucokinase isoform X1 [KO:K12407] [EC:2.7.1.2]
112405403  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
112405442  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
112405497  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
112394271  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
112408582  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
112400986  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
112392966  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
112410900  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
112393810  PDHA2; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
112394989  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
112400505  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
112410744  LDHAL6B; LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
112412913  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
112401637  LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
112391777  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
nasi00010  Glycolysis / Gluconeogenesis
nasi00020  Citrate cycle (TCA cycle)
nasi00061  Fatty acid biosynthesis
nasi00190  Oxidative phosphorylation
nasi04020  Calcium signaling pathway
nasi04024  cAMP signaling pathway
nasi04068  FoxO signaling pathway
nasi04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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