KEGG   PATHWAY: pgig04922
Entry
pgig04922                   Pathway                                
Name
Glucagon signaling pathway - Pteropus giganteus (Indian flying fox)
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
pgig04922  Glucagon signaling pathway
pgig04922

Organism
Pteropus giganteus (Indian flying fox) [GN:pgig]
Gene
120613959  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120595669  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120619079  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120603240  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
120596948  GCG; pro-glucagon isoform X1 [KO:K05259]
120600071  GCGR; LOW QUALITY PROTEIN: glucagon receptor [KO:K04583]
120603881  neuroendocrine secretory protein 55-like [KO:K04632]
120603882  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
120586284  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
120583269  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
120618485  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
120587583  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
120597156  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
120602997  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
120592160  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
120615385  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
120606645  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
120601151  CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
120612863  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
120602391  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
120619611  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
120621628  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
120598454  serine/threonine-protein phosphatase 4 regulatory subunit 3-B-like [KO:K17491]
120620123  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
120592226  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
120621981  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
120602971  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
120620322  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
120582783  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
120598582  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
120588271  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120587190  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120600630  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
120611916  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
120611973  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
120582429  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
120618337  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
120597599  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
120591098  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120606631  PPP3CC; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
120609542  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120594548  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
120596960  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
120581548  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
120609540  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120589350  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
120589558  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
120583890  FOXO1; forkhead box protein O1 [KO:K07201]
120609435  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
120602869  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
120615542  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
120596847  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
120589204  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
120611062  G6PC1; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
120603862  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
120608500  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
120584729  CPT1A; LOW QUALITY PROTEIN: carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
120602813  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
120615532  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
120606948  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
120618372  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
120594298  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
120617236  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
120585413  PHKA1; LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
120591810  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
120620078  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
120604475  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
120617886  CALM3; calmodulin-3 [KO:K02183]
120619605  CALM1; calmodulin-1 [KO:K02183]
120608993  calmodulin-alpha-like isoform X1 [KO:K02183]
120621675  CALM2; calmodulin-2 isoform X1 [KO:K02183]
120604438  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
120586970  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
120600705  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
120593543  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
120586161  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
120621730  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
120606777  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
120585136  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
120618205  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
120587666  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
120601493  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
120621151  ACACA; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
120601871  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
120607180  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299]
120604383  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
120589556  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
120616910  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
120616911  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
120618224  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
120598551  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
120609674  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
120609248  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
120589553  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
120597892  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
120594235  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
120587979  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
120599500  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
120604536  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
120604563  L-lactate dehydrogenase C chain-like [KO:K00016] [EC:1.1.1.27]
120618368  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
120611412  LDHAL6B; L-lactate dehydrogenase A-like 6B [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
pgig00010  Glycolysis / Gluconeogenesis
pgig00020  Citrate cycle (TCA cycle)
pgig00061  Fatty acid biosynthesis
pgig00190  Oxidative phosphorylation
pgig04020  Calcium signaling pathway
pgig04024  cAMP signaling pathway
pgig04068  FoxO signaling pathway
pgig04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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