KEGG   PATHWAY: prob04922
Entry
prob04922                   Pathway                                
Name
Glucagon signaling pathway - Phodopus roborovskii (desert hamster)
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
prob04922  Glucagon signaling pathway
prob04922

Organism
Phodopus roborovskii (desert hamster) [GN:prob]
Gene
127223664  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127231187  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127239025  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127228213  Pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
127222478  Gcg; pro-glucagon isoform X1 [KO:K05259]
127220317  Gcgr; LOW QUALITY PROTEIN: glucagon receptor [KO:K04583]
127222868  neuroendocrine secretory protein 55-like [KO:K04632]
127222787  Gnas; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
127220711  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
127229872  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
127229917  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
127226375  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
127222404  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
127225814  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
127222230  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
127216557  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
127217490  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
127224594  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
127232866  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
127214253  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
127235522  Creb5; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 5 [KO:K09047]
127218549  protein PPP4R3C [KO:K17491]
127231071  Ppp4r3a; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
127234011  Ppp4r3b; serine/threonine-protein phosphatase 4 regulatory subunit 3B [KO:K17491]
127228346  Ppp4c; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
127232977  Crtc2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
127231726  Sik2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
127219616  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
127225831  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
127213598  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
127224168  Sik1; LOW QUALITY PROTEIN: serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
127229038  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
127228774  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
127221390  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
127221392  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
127221647  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
127236214  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127213143  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127224232  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127222969  Ppp3ca; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
127230207  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127214138  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127224691  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
127233971  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
127223054  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
127214148  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
127233865  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
127234052  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
127216298  Foxo1; forkhead box protein O1 [KO:K07201]
127224056  Sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
127225913  Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
127213732  Prmt1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
127221880  G6pc2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
127216693  G6pc1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
127217401  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
127222798  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
127230385  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
127228604  Cpt1a; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
127225959  Cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
127213870  Cpt1c; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
127215592  LOW QUALITY PROTEIN: glycogen [starch] synthase, liver-like [KO:K00693] [EC:2.4.1.11]
127213091  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
127213697  Gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
127229936  Phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
127217902  Phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
127217938  Phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
127228393  Phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
127237009  Phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
127223580  calmodulin-alpha-like [KO:K02183]
127229809  calmodulin-like protein 3 [KO:K02183]
127229810  Calml5; calmodulin-like protein 5 [KO:K02183]
127231063  Calm1; calmodulin-1 [KO:K02183]
127231862  Calml4; calmodulin-like protein 4 [KO:K02183]
127238587  Calm3; calmodulin-3 [KO:K02183]
127213474  Calml6; calmodulin-like protein 6 [KO:K02183]
127214928  Calm2; calmodulin-2 [KO:K02183]
127228731  Pygm; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
127228866  Pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
127230657  Pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
127217948  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
127224997  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
127220610  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
127216002  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
127233006  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
127235796  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
127226041  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
127226445  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
127221108  Acaca; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
127215967  Acacb; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
127225264  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
127223358  Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
127233921  Gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
127229132  Fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
127229133  Fbp1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
127229794  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
127224156  Pfkl; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
127226018  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
127237556  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
127238064  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
127233316  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
127233974  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
127234367  LOW QUALITY PROTEIN: pyruvate kinase PKM-like [KO:K00873] [EC:2.7.1.40]
127229369  pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
127217899  Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
127230144  pyruvate dehydrogenase E1 component subunit beta, mitochondrial-like [KO:K00162] [EC:1.2.4.1]
127238207  Pdhb; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
127237742  Ldhal6b; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
127213088  Ldhb; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
127213694  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
127213718  L-lactate dehydrogenase A 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
prob00010  Glycolysis / Gluconeogenesis
prob00020  Citrate cycle (TCA cycle)
prob00061  Fatty acid biosynthesis
prob00190  Oxidative phosphorylation
prob04020  Calcium signaling pathway
prob04024  cAMP signaling pathway
prob04068  FoxO signaling pathway
prob04910  Insulin signaling pathway
KO pathway
ko04922   
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