ENTRY ko04922 Pathway NAME Glucagon signaling pathway 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 ko04922 Glucagon signaling pathway ORTHOLOGY K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] K13296 cGMP-inhibited 3',5'-cyclic phosphodiesterase B [EC:3.1.4.17] K05259 glucagon K04583 glucagon receptor K04632 guanine nucleotide-binding protein G(s) subunit alpha K08042 adenylate cyclase 2 [EC:4.6.1.1] K04345 protein kinase A [EC:2.7.11.11] K05870 cyclic AMP-responsive element-binding protein 1 K04450 cyclic AMP-dependent transcription factor ATF-2 K04374 cyclic AMP-dependent transcription factor ATF-4 K09048 cyclic AMP-responsive element-binding protein 3 K09047 cyclic AMP-responsive element-binding protein 5 K17491 protein phosphatase 4 regulatory subunit 3 K15423 serine/threonine-protein phosphatase 4 catalytic subunit [EC:3.1.3.16] K16333 CREB-regulated transcription coactivator 2 K16311 serine/threonine-protein kinase SIK2 [EC:2.7.11.1] K04498 E1A/CREB-binding protein [EC:2.3.1.48] K07202 alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha K19008 serine/threonine-protein kinase SIK1 [EC:2.7.11.1] K04634 guanine nucleotide-binding protein G(q) subunit alpha K05858 phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K04958 inositol 1,4,5-triphosphate receptor type 1 K04959 inositol 1,4,5-triphosphate receptor type 2 K04960 inositol 1,4,5-triphosphate receptor type 3 K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] K06268 serine/threonine-protein phosphatase 2B regulatory subunit K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] K07201 forkhead box protein O1 K11411 NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286] K07294 peroxisome proliferator-activated receptor alpha K11434 type I protein arginine methyltransferase [EC:2.1.1.319] K01084 glucose-6-phosphatase [EC:3.1.3.9] K01596 phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32] K08765 carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21] K19523 carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21] K19524 carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21] K00693 glycogen synthase [EC:2.4.1.11] K07190 phosphorylase kinase alpha/beta subunit K00871 phosphorylase kinase gamma subunit [EC:2.7.11.19] K02183 calmodulin K00688 glycogen phosphorylase [EC:2.4.1.1] K19028 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 1 [EC:2.7.1.105 3.1.3.46] K07198 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K07199 5'-AMP-activated protein kinase, regulatory beta subunit K07200 5'-AMP-activated protein kinase, regulatory gamma subunit K11262 acetyl-CoA carboxylase / biotin carboxylase 1 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K01946 acetyl-CoA carboxylase / biotin carboxylase 2 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K07299 MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1 K07593 MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 2 K12407 glucokinase [EC:2.7.1.2] K03841 fructose-1,6-bisphosphatase I [EC:3.1.3.11] K00850 6-phosphofructokinase 1 [EC:2.7.1.11] K01834 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase [EC:5.4.2.11] K00873 pyruvate kinase [EC:2.7.1.40] K00161 pyruvate dehydrogenase E1 component subunit alpha [EC:1.2.4.1] K00162 pyruvate dehydrogenase E1 component subunit beta [EC:1.2.4.1] K00016 L-lactate dehydrogenase [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. 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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. 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JOURNAL Nature 485:128-32 (2012) DOI:10.1038/nature10988 REL_PATHWAY ko00010 Glycolysis / Gluconeogenesis ko00020 Citrate cycle (TCA cycle) ko00061 Fatty acid biosynthesis ko00190 Oxidative phosphorylation ko04020 Calcium signaling pathway ko04024 cAMP signaling pathway ko04068 FoxO signaling pathway ko04910 Insulin signaling pathway ///