KEGG   PATHWAY: llv04922
Entry
llv04922                    Pathway                                
Name
Glucagon signaling pathway - Lutra lutra (Eurasian river otter)
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
llv04922  Glucagon signaling pathway
llv04922

Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125086439  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125104283  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125089561  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125078327  cGMP-inhibited 3',5'-cyclic phosphodiesterase B-like isoform X1 [KO:K13296] [EC:3.1.4.17]
125095827  pro-glucagon isoform X1 [KO:K05259]
125087906  glucagon receptor-like isoform X1 [KO:K04583]
125108178  neuroendocrine secretory protein 55 [KO:K04632]
125108177  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
125099871  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
125083608  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
125097539  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125095039  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
125095761  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
125106338  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125083953  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
125085653  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
125086626  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
125079521  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
125080714  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
125080867  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
125091806  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
125108888  serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
125103989  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
125090980  serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
125085649  CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
125078653  serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
125091150  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
125106189  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
125093590  peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
125093647  serine/threonine-protein kinase SIK1-like isoform X1 [KO:K19008] [EC:2.7.11.1]
125083151  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
125108695  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
125108926  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125110237  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
125105190  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125109360  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125107116  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125103123  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
125084662  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2B catalytic subunit beta isoform-like [KO:K04348] [EC:3.1.3.16]
125092859  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
125093220  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
125083501  calcineurin subunit B type 2 [KO:K06268]
125100120  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
125084354  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
125093303  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
125080735  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
125096352  forkhead box protein O1 isoform X1 [KO:K07201]
125084753  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
125106785  peroxisome proliferator-activated receptor alpha [KO:K07294]
125089300  LOW QUALITY PROTEIN: protein arginine N-methyltransferase 1-like [KO:K11434] [EC:2.1.1.319]
125108890  LOW QUALITY PROTEIN: glucose-6-phosphatase 3-like [KO:K01084] [EC:3.1.3.9]
125086776  glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
125087871  glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
125096440  glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
125109569  phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
125104311  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
125078256  carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
125106776  carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
125089298  LOW QUALITY PROTEIN: carnitine O-palmitoyltransferase 1, brain isoform-like [KO:K19524] [EC:2.3.1.21]
125107979  glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
125089398  glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
125091601  phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
125091894  LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform-like [KO:K07190]
125089982  phosphorylase b kinase regulatory subunit beta [KO:K07190]
125090418  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
125090709  phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
125099896  calmodulin-1-like [KO:K02183]
125107709  calmodulin-like protein 3 [KO:K02183]
125092830  calmodulin-1 [KO:K02183]
125109105  calmodulin-1 [KO:K02183]
125104272  calmodulin-like protein 4 isoform X1 [KO:K02183]
125104293  calmodulin-1 [KO:K02183]
125097034  calmodulin-like protein 6 [KO:K02183]
125097532  calmodulin-1-like [KO:K02183]
125089454  calmodulin-1 [KO:K02183]
125108425  glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
125078502  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
125104981  LOW QUALITY PROTEIN: glycogen phosphorylase, liver form-like [KO:K00688] [EC:2.4.1.1]
125082434  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
125100268  5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
125096749  5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
125097369  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
125081898  5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
125096032  5'-AMP-activated protein kinase subunit gamma-3-like isoform X1 [KO:K07200]
125080474  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
125107078  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
125087711  acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125081691  acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125097900  solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
125100360  solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
125081245  hexokinase-4 [KO:K12407] [EC:2.7.1.2]
125083640  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
125083850  fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
125107773  ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
125107931  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
125093473  ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
125085109  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
125080724  phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
125105357  pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
125091627  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
125094265  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
125078360  pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
125092209  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
125109100  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
125109539  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
125093622  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
125102305  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
125078725  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
125078726  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
125095937  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
125095952  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
125095981  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
125105385  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
125107199  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
llv00010  Glycolysis / Gluconeogenesis
llv00020  Citrate cycle (TCA cycle)
llv00061  Fatty acid biosynthesis
llv00190  Oxidative phosphorylation
llv04020  Calcium signaling pathway
llv04024  cAMP signaling pathway
llv04068  FoxO signaling pathway
llv04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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