KEGG   PATHWAY: hgl04922
Entry
hgl04922                    Pathway                                
Name
Glucagon signaling pathway - Heterocephalus glaber (naked mole-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
hgl04922  Glucagon signaling pathway
hgl04922

Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101700695  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
101719164  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
101701289  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
101724440  Pde3b; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
101722590  Gcg; glucagon [KO:K05259]
101708959  Gcgr; glucagon receptor [KO:K04583]
101716905  Gnas; GNAS complex locus [KO:K04632]
101705689  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
101718304  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101707235  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101721558  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101712503  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
101717365  Atf2; activating transcription factor 2 [KO:K04450]
101724287  Atf4; activating transcription factor 4 [KO:K04374]
101715715  Creb3l2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
101698748  Creb3l1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
101716023  Creb3l3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
101706643  Creb3l4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
101718447  Creb3; cAMP responsive element binding protein 3 [KO:K09048]
101703315  Creb5; cAMP responsive element binding protein 5 [KO:K09047]
101710488  Ppp4r3a; protein phosphatase 4 regulatory subunit 3A [KO:K17491]
101706954  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
101706307  serine/threonine-protein phosphatase 4 regulatory subunit 3B [KO:K17491]
101706981  Ppp4r3b; protein phosphatase 4 regulatory subunit 3B [KO:K17491]
101701412  Ppp4c; protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
101709168  Crtc2; CREB regulated transcription coactivator 2 [KO:K16333]
101724122  Sik2; salt inducible kinase 2 [KO:K16311] [EC:2.7.11.1]
101711512  Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
101714025  Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
101703716  Ppargc1a; PPARG coactivator 1 alpha [KO:K07202]
101702040  Sik1; salt inducible kinase 1 [KO:K19008] [EC:2.7.11.1]
101715420  Gnaq; G protein subunit alpha q [KO:K04634]
101725860  Plcb1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101696454  Plcb4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101697744  Plcb3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
101708380  Plcb2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101706047  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101716022  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101706978  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101708178  Ppp3cb; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
101719947  Ppp3cc; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
101698959  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
101706255  Ppp3r1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
101710684  Ppp3r2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
101718749  Camk2b; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
101713923  Camk2g; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
101722229  Camk2a; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
101711305  Camk2d; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
101707441  Foxo1; forkhead box O1 [KO:K07201]
101720282  Sirt1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
101725514  Ppara; peroxisome proliferator activated receptor alpha [KO:K07294]
101721462  Prmt1; protein arginine methyltransferase 1 [KO:K11434] [EC:2.1.1.319]
101715644  G6pc2; glucose-6-phosphatase catalytic subunit 2 [KO:K01084] [EC:3.1.3.9]
101708598  G6pc; glucose-6-phosphatase catalytic subunit [KO:K01084] [EC:3.1.3.9]
101723886  G6pc3; glucose-6-phosphatase catalytic subunit 3 [KO:K01084] [EC:3.1.3.9]
101708730  Pck1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32]
101706336  Pck2; phosphoenolpyruvate carboxykinase 2, mitochondrial [KO:K01596] [EC:4.1.1.32]
101716055  Cpt1a; carnitine palmitoyltransferase 1A [KO:K08765] [EC:2.3.1.21]
101724285  Cpt1b; carnitine palmitoyltransferase 1B [KO:K19523] [EC:2.3.1.21]
101719936  Cpt1c; carnitine palmitoyltransferase 1C [KO:K19524] [EC:2.3.1.21]
101699800  Gys2; glycogen synthase 2 [KO:K00693] [EC:2.4.1.11]
101712358  Gys1; glycogen synthase 1 [KO:K00693] [EC:2.4.1.11]
101699364  Phka1; phosphorylase kinase regulatory subunit alpha 1 [KO:K07190]
101706280  Phkb; phosphorylase kinase regulatory subunit beta [KO:K07190]
101713572  Phka2; phosphorylase kinase regulatory subunit alpha 2 [KO:K07190]
101707775  Phkg1; phosphorylase kinase catalytic subunit gamma 1 [KO:K00871] [EC:2.7.11.19]
101700591  Phkg2; phosphorylase kinase catalytic subunit gamma 2 [KO:K00871] [EC:2.7.11.19]
101704751  Calm2; calmodulin 2 [KO:K02183]
101713746  Calm1; calmodulin 1 [KO:K02183]
101724181  Calm3; calmodulin 3 [KO:K02183]
101716865  Calml3; calmodulin like 3 [KO:K02183]
101725309  Calml5; calmodulin like 5 [KO:K02183]
101714220  calmodulin-like [KO:K02183]
101712577  Calml6; calmodulin like 6 [KO:K02183]
101707626  Calml4; calmodulin like 4 [KO:K02183]
101723998  Pygl; glycogen phosphorylase L [KO:K00688] [EC:2.4.1.1]
101717341  Pygb; glycogen phosphorylase B [KO:K00688] [EC:2.4.1.1]
101713354  Pygm; glycogen phosphorylase, muscle associated [KO:K00688] [EC:2.4.1.1]
101701867  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
101698482  Prkaa2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
101722998  Prkaa1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
101705863  Prkab1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
101720100  Prkab2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
101699641  Prkag2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
101699667  Prkag3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
101721085  Prkag1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
101706028  Acaca; acetyl-CoA carboxylase alpha [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101717399  Acacb; acetyl-CoA carboxylase beta [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101697875  Slc2a1; solute carrier family 2 member 1 [KO:K07299]
101699012  Slc2a2; solute carrier family 2 member 2 [KO:K07593]
101721664  Gck; glucokinase [KO:K12407] [EC:2.7.1.2]
101707693  Fbp2; fructose-bisphosphatase 2 [KO:K03841] [EC:3.1.3.11]
101708632  Fbp1; fructose-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101724978  Pfkl; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
101709405  Pfkp; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
101705614  Pfkm; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
101725467  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
101723534  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101704135  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
101714576  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
101721034  Pkm; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
101710793  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
101716937  Pdha1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
101714134  Pdhb; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
101699088  Ldhb; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
101715364  Ldha; lactate dehydrogenase A [KO:K00016] [EC:1.1.1.27]
101715932  Ldhc; lactate dehydrogenase C [KO:K00016] [EC:1.1.1.27]
101703298  Ldhal6b; lactate dehydrogenase A like 6B [KO:K00016] [EC:1.1.1.27]
101724420  L-lactate dehydrogenase A 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
hgl00010  Glycolysis / Gluconeogenesis
hgl00020  Citrate cycle (TCA cycle)
hgl00061  Fatty acid biosynthesis
hgl00190  Oxidative phosphorylation
hgl04020  Calcium signaling pathway
hgl04024  cAMP signaling pathway
hgl04068  FoxO signaling pathway
hgl04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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