KEGG   PATHWAY: rno04922
Entry
rno04922                    Pathway                                
Name
Glucagon signaling pathway - Rattus norvegicus (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
rno04922  Glucagon signaling pathway
rno04922

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29516  Pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
24952  Gcg; pro-glucagon preproprotein [KO:K05259]
24953  Gcgr; glucagon receptor precursor [KO:K04583]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
81647  Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
79255  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
310616  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
362165  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
362339  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
314638  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
500131  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
100909486  Ppp4r3cl3; protein PPP4R3C-like [KO:K17491]
302447  Ppp4r3cl2; protein PPP4R3C [KO:K17491]
302756  Ppp4r3c; protein phosphatase 4 regulatory subunit 3C [KO:K17491]
314388  Ppp4r3a; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform 2 [KO:K17491]
317272  Ppp4r3cl1; protein PPP4R3C [KO:K17491]
360993  Ppp4r3b; serine/threonine-protein phosphatase 4 regulatory subunit 3B [KO:K17491]
171366  Ppp4c; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
310615  Crtc2; CREB-regulated transcription coactivator 2 [KO:K16333]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
83516  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
59329  Sik1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
25400  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
24246  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
24245  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515] [EC:2.7.11.17]
171140  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
84482  Foxo1; forkhead box protein O1 [KO:K07201]
309757  Sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
25747  Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
60421  Prmt1; protein arginine N-methyltransferase 1 [KO:K11434] [EC:2.1.1.319]
100361025  Prmt1l1; protein arginine N-methyltransferase 1-like [KO:K11434] [EC:2.1.1.319]
25634  G6pc1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
303565  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
362282  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
361042  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
25757  Cpt1a; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
25756  Cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
308579  Cpt1c; palmitoyl thioesterase CPT1C [KO:K19524] [EC:2.3.1.21]
25623  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
690987  Gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
64561  Phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
361377  Phkb; phosphorylase b kinase regulatory subunit beta isoform 1 [KO:K07190]
678739  Phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
140671  Phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
29353  Phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
50663  Calm2; calmodulin-2 [KO:K02183]
64035  Pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
25739  Pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
24701  Pygm; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
24638  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
65248  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
78975  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
83803  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
64562  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
25520  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
301518  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
60581  Acaca; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116719  Acacb; acetyl-CoA carboxylase 2 precursor [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
24778  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
25351  Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
24385  Gck; hexokinase-4 isoform 2 [KO:K12407] [EC:2.7.1.2]
24362  Fbp1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
114508  Fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
65152  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
25741  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
60416  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
24642  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
24959  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
25630  Pkm; pyruvate kinase PKM [KO:K00873] [EC:2.7.1.40]
100362738  Pkml1; pyruvate kinase PKM-like [KO:K00873] [EC:2.7.1.40]
117098  Pdha2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial precursor [KO:K00161] [EC:1.2.4.1]
29554  Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial precursor [KO:K00161] [EC:1.2.4.1]
289950  Pdhb; pyruvate dehydrogenase E1 component subunit beta, mitochondrial precursor [KO:K00162] [EC:1.2.4.1]
24533  Ldha; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
24534  Ldhb; L-lactate dehydrogenase B chain isoform Ldhb [KO:K00016] [EC:1.1.1.27]
29634  Ldhc; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
369018  Ldhal6b; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
500965  Ldhal1; L-lactate dehydrogenase A chain-like [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
rno00010  Glycolysis / Gluconeogenesis
rno00020  Citrate cycle (TCA cycle)
rno00061  Fatty acid biosynthesis
rno00190  Oxidative phosphorylation
rno04020  Calcium signaling pathway
rno04024  cAMP signaling pathway
rno04068  FoxO signaling pathway
rno04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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