KEGG   PATHWAY: cjc04911
Entry
cjc04911                    Pathway                                

Name
Insulin secretion - Callithrix jacchus (white-tufted-ear marmoset)
Description
Pancreatic beta cells are specialised endocrine cells that continuously sense the levels of blood sugar and other fuels and, in response, secrete insulin to maintain normal fuel homeostasis. Glucose-induced insulin secretion and its potentiation constitute the principal mechanism of insulin release. Glucose is transported by the glucose transporter (GLUT) into the pancreatic beta-cell. Metabolism of glucose generates ATP, which inhibits ATP-sensitive K+ channels and causes voltage-dependent Ca2+ influx. Elevation of [Ca2+]i triggers exocytotic release of insulin granules. Insulin secretion is further regulated by several hormones and neurotransmitters. Peptide hormones, such as glucagon-like peptide 1 (GLP-1), increase cAMP levels and thereby potentiate insulin secretion via the combined action of PKA and Epac2. Achetylcholine (ACh), a major parasympathetic neurotransmitter, binds to Gq-coupled receptors and activates phospholipase C- (PLC-), and the stimulatory effects involve activation of protein kinase C (PKC), which stimulates exocytosis. In addition, ACh mobilizes intracellular Ca2+ by activation of IP3 receptors.
Class
Organismal Systems; Endocrine system
Pathway map
cjc04911  Insulin secretion
cjc04911

Other DBs
GO: 0030073
Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100404544  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
100397713  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
100409392  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
100408384  TRPM4; transient receptor potential cation channel subfamily M member 4 [KO:K04979]
100410682  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
100402438  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
100403160  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100393318  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
100414358  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
100412553  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
100392174  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
103794919  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
103796045  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
100386093  ABCC8; ATP binding cassette subfamily C member 8 [KO:K05032]
100401039  KCNJ11; potassium voltage-gated channel subfamily J member 11 [KO:K05004]
100406735  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
100397940  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
100386041  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
100390112  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
100397956  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
100405903  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
100391424  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
100390938  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
100410352  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
100402638  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
100394787  KCNU1; potassium calcium-activated channel subfamily U member 1 [KO:K05274]
100395410  KCNMB1; potassium calcium-activated channel subfamily M regulatory beta subunit 1 [KO:K04937]
100394193  KCNMB2; potassium calcium-activated channel subfamily M regulatory beta subunit 2 [KO:K04938]
100403137  KCNMB3; potassium calcium-activated channel subfamily M regulatory beta subunit 3 [KO:K04939]
100413100  KCNMB4; potassium calcium-activated channel subfamily M regulatory beta subunit 4 [KO:K04941]
100398217  KCNN1; potassium calcium-activated channel subfamily N member 1 [KO:K04942]
100413033  KCNN2; potassium calcium-activated channel subfamily N member 2 [KO:K04943]
100387208  KCNN3; potassium calcium-activated channel subfamily N member 3 [KO:K04944]
100391934  KCNN4; potassium calcium-activated channel subfamily N member 4 [KO:K04945]
100399074  GCG; glucagon [KO:K05259]
100394829  GLP1R; glucagon like peptide 1 receptor [KO:K04581]
100396171  GIP; gastric inhibitory polypeptide [KO:K05258]
100387965  GPR119; G protein-coupled receptor 119 [KO:K08424]
100390670  ADCYAP1; adenylate cyclase activating polypeptide 1 [KO:K05262]
100387025  ADCYAP1R1; ADCYAP receptor type I [KO:K04587]
100408515  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103787209  neuroendocrine secretory protein 55 [KO:K04632]
100394265  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100385658  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100415165  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100415141  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100412782  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100406617  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
100404620  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100404484  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100405403  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100392123  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
100407753  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100408115  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
100407692  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100400737  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100407681  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
100414156  ATF2; activating transcription factor 2 [KO:K04450]
100392193  ATF4; activating transcription factor 4 [KO:K04374]
100394351  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
100408954  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
100406635  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
100411140  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
100409637  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
100392579  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
100411862  ATF6B; activating transcription factor 6 beta [KO:K09049]
100404648  PDX1; pancreatic and duodenal homeobox 1 [KO:K07594]
100393089  INS; insulin [KO:K04526]
100401754  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
100390099  RIMS2; regulating synaptic membrane exocytosis 2 [KO:K15297]
100388471  PCLO; piccolo presynaptic cytomatrix protein [KO:K16882]
100407777  RAB3A; RAB3A, member RAS oncogene family [KO:K07882]
100396125  CCK; cholecystokinin [KO:K05226]
100403390  CCKAR; cholecystokinin A receptor [KO:K04194]
100408980  CHRM3; cholinergic receptor muscarinic 3 [KO:K04131]
100410637  FFAR1; free fatty acid receptor 1 [KO:K04325]
100403006  GNAQ; G protein subunit alpha q [KO:K04634]
100386734  GNA11; G protein subunit alpha 11 [KO:K04635]
100400803  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100386921  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100409716  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100410075  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100390843  inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
100406916  RYR2; ryanodine receptor 2 [KO:K04962]
100410194  VAMP2; vesicle associated membrane protein 2 [KO:K13504]
100399018  STX1A; syntaxin 1A [KO:K04560]
100413178  SNAP25; synaptosome associated protein 25 [KO:K18211]
100391814  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
100410136  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
100404028  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
Compound
C00002  ATP
C00022  Pyruvate
C00031  D-Glucose
C00076  Calcium cation
C00092  D-Glucose 6-phosphate
C00162  Fatty acid
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01996  Acetylcholine
Reference
  Authors
Seino S, Shibasaki T, Minami K
  Title
Pancreatic beta-cell signaling: toward better understanding of diabetes and its treatment.
  Journal
Proc Jpn Acad Ser B Phys Biol Sci 86:563-77 (2010)
DOI:10.2183/pjab.86.563
Reference
  Authors
Jitrapakdee S, Wutthisathapornchai A, Wallace JC, MacDonald MJ
  Title
Regulation of insulin secretion: role of mitochondrial signalling.
  Journal
Diabetologia 53:1019-32 (2010)
DOI:10.1007/s00125-010-1685-0
Reference
  Authors
Rorsman P, Braun M
  Title
Regulation of insulin secretion in human pancreatic islets.
  Journal
Annu Rev Physiol 75:155-79 (2013)
DOI:10.1146/annurev-physiol-030212-183754
Reference
PMID:9715374
  Authors
Jones PM, Persaud SJ
  Title
Protein kinases, protein phosphorylation, and the regulation of insulin secretion from pancreatic beta-cells.
  Journal
Endocr Rev 19:429-61 (1998)
DOI:10.1210/edrv.19.4.0339
Reference
  Authors
MacDonald PE
  Title
Signal integration at the level of ion channel and exocytotic function in pancreatic beta-cells.
  Journal
Am J Physiol Endocrinol Metab 301:E1065-9 (2011)
DOI:10.1152/ajpendo.00426.2011
Reference
PMID:9914469
  Authors
Lang J
  Title
Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion.
  Journal
Eur J Biochem 259:3-17 (1999)
DOI:10.1046/j.1432-1327.1999.00043.x
Reference
  Authors
Kieffer TJ, Habener JF
  Title
The glucagon-like peptides.
  Journal
Endocr Rev 20:876-913 (1999)
DOI:10.1210/edrv.20.6.0385
Reference
  Authors
Girard J
  Title
The incretins: from the concept to their use in the treatment of type 2 diabetes. Part A: incretins: concept and physiological functions.
  Journal
Diabetes Metab 34:550-9 (2008)
DOI:10.1016/j.diabet.2008.09.001
Reference
  Authors
Holz GG
  Title
New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells.
  Journal
Horm Metab Res 36:787-94 (2004)
DOI:10.1055/s-2004-826165
Reference
  Authors
Holst JJ, Gromada J
  Title
Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans.
  Journal
Am J Physiol Endocrinol Metab 287:E199-206 (2004)
DOI:10.1152/ajpendo.00545.2003
Reference
  Authors
Doyle ME, Egan JM
  Title
Mechanisms of action of glucagon-like peptide 1 in the pancreas.
  Journal
Pharmacol Ther 113:546-93 (2007)
DOI:10.1016/j.pharmthera.2006.11.007
Reference
  Authors
Kim W, Egan JM
  Title
The role of incretins in glucose homeostasis and diabetes treatment.
  Journal
Pharmacol Rev 60:470-512 (2008)
DOI:10.1124/pr.108.000604
Reference
  Authors
Seino S, Takahashi H, Fujimoto W, Shibasaki T
  Title
Roles of cAMP signalling in insulin granule exocytosis.
  Journal
Diabetes Obes Metab 11 Suppl 4:180-8 (2009)
DOI:10.1111/j.1463-1326.2009.01108.x
Reference
  Authors
Tengholm A
  Title
Cyclic AMP dynamics in the pancreatic beta-cell.
  Journal
Ups J Med Sci 117:355-69 (2012)
DOI:10.3109/03009734.2012.724732
Reference
  Authors
Holz GG
  Title
Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell.
  Journal
Diabetes 53:5-13 (2004)
DOI:10.2337/diabetes.53.1.5
Reference
  Authors
Gloerich M, Bos JL
  Title
Epac: defining a new mechanism for cAMP action.
  Journal
Annu Rev Pharmacol Toxicol 50:355-75 (2010)
DOI:10.1146/annurev.pharmtox.010909.105714
Reference
  Authors
Bos JL
  Title
Epac proteins: multi-purpose cAMP targets.
  Journal
Trends Biochem Sci 31:680-6 (2006)
DOI:10.1016/j.tibs.2006.10.002
Reference
  Authors
Filipsson K, Kvist-Reimer M, Ahren B
  Title
The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet function.
  Journal
Diabetes 50:1959-69 (2001)
DOI:10.2337/diabetes.50.9.1959
Reference
  Authors
Kebede MA, Alquier T, Latour MG, Poitout V
  Title
Lipid receptors and islet function: therapeutic implications?
  Journal
Diabetes Obes Metab 11 Suppl 4:10-20 (2009)
DOI:10.1111/j.1463-1326.2009.01114.x
Reference
  Authors
Morgan NG, Dhayal S
  Title
G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell.
  Journal
Biochem Pharmacol 78:1419-27 (2009)
DOI:10.1016/j.bcp.2009.07.020
Related
pathway
cjc00020  Citrate cycle (TCA cycle)
cjc04020  Calcium signaling pathway
cjc05211  Renal cell carcinoma
KO pathway
ko04911   
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