KEGG   PATHWAY: anu04922
Entry
anu04922                    Pathway                                
Name
Glucagon signaling pathway - Arvicanthis niloticus (African grass rat)
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
anu04922  Glucagon signaling pathway
anu04922

Organism
Arvicanthis niloticus (African grass rat) [GN:anu]
Gene
117697536  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117706636  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117721481  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117696410  Pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
117704397  Gcg; glucagon isoform X1 [KO:K05259]
117711212  Gcgr; glucagon receptor [KO:K04583]
117703732  neuroendocrine secretory protein 55 [KO:K04632]
117703734  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
117723703  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
117723055  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117706647  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117705049  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
117703314  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
117719125  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117704442  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
117707799  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
117709015  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
117720532  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
117696466  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
117720600  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
117697219  Ppp4r3a; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
117712656  Ppp4r3b; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
117693953  LOW QUALITY PROTEIN: protein PPP4R3C-like [KO:K17491]
117694049  protein PPP4R3C-like [KO:K17491]
117694925  protein PPP4R3C-like [KO:K17491]
117695312  protein PPP4R3C-like [KO:K17491]
117695349  protein PPP4R3C-like [KO:K17491]
117695531  protein PPP4R3C-like [KO:K17491]
117724803  Ppp4c; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
117706666  Crtc2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
117699504  Sik2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
117718741  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117710697  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117712664  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
117724618  Sik1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
117705469  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
117712005  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
117703017  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
117703351  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
117703529  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
117714720  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
117714743  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
117724336  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
117705132  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117705334  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117706625  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117712605  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
117701820  calcineurin subunit B type 1-like [KO:K06268]
117709539  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
117705311  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
117707719  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
117719604  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
117713012  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
117706979  Foxo1; forkhead box protein O1 [KO:K07201]
117724644  Sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
117718753  Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
117713805  Prmt1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
117711869  G6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
117709844  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
117704199  G6pc2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
117706152  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
117703545  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
117704625  Cpt1a; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
117718598  Cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
117719424  Cpt1c; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
117714877  Gys1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
117715222  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
117723492  Phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
117694487  Phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
117695387  Phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
117714976  Phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
117697985  Phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
117722538  calmodulin-1-like [KO:K02183]
117697522  Calm1; calmodulin-1 [KO:K02183]
117715216  calmodulin-1-like [KO:K02183]
117716931  Calm2; calmodulin-2 [KO:K02183]
117699053  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
117700456  Calm3; calmodulin-3 [KO:K02183]
117713333  Calml3; calmodulin-like protein 3 [KO:K02183]
117713892  Calml5; calmodulin-like protein 5 [KO:K02183]
117704513  Pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
117717246  Pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
117709985  Pygm; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
117717084  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1-like isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
117694333  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
117723868  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
117708512  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
117698037  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
117707094  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
117705444  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
117719091  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
117720702  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
117709906  Acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117698256  Acacb; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117708410  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
117707535  Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
117712800  Gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
117713746  Fbp1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
117713747  Fbp2; fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
117724408  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
117719354  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
117713608  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
117715373  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
117712501  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
117699104  Pkm; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
117720999  LOW QUALITY PROTEIN: pyruvate kinase PKM-like [KO:K00873] [EC:2.7.1.40]
117707610  Pdha2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
117700952  LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
117701853  LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
117694157  Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
117705012  Pdhb; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
117704444  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
117714782  Ldhb; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
117717083  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
117700043  L-lactate dehydrogenase A-like 6A isoform X1 [KO:K00016] [EC:1.1.1.27]
117708312  Ldha; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
117712847  L-lactate dehydrogenase C chain 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
anu00010  Glycolysis / Gluconeogenesis
anu00020  Citrate cycle (TCA cycle)
anu00061  Fatty acid biosynthesis
anu00190  Oxidative phosphorylation
anu04020  Calcium signaling pathway
anu04024  cAMP signaling pathway
anu04068  FoxO signaling pathway
anu04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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