KEGG   PATHWAY: dnm04911
Entry
dnm04911                    Pathway                                
Name
Insulin secretion - Dasypus novemcinctus (nine-banded armadillo)
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
dnm04911  Insulin secretion
dnm04911

Other DBs
GO: 0030073
Organism
Dasypus novemcinctus (nine-banded armadillo) [GN:dnm]
Gene
101411329  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
101415775  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101422600  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101435288  solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101433314  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101441311  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101427108  solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101443849  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101426792  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101444965  solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101412484  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101443104  solute carrier family 2, facilitated glucose transporter member 2-like isoform X1 [KO:K07593]
101439289  solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
101442210  solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101420912  solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101447085  solute carrier family 2, facilitated glucose transporter member 2-like [KO:K07593]
101429195  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
101422147  TRPM4; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 4 [KO:K04979]
101416281  ATP1A1; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
101444307  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
101445509  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
101413464  sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
101438577  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
101412342  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
101412798  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
101415633  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
101437876  ATP-binding cassette sub-family C member 8 isoform X1 [KO:K05032]
101438610  KCNJ11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004]
101431301  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X9 [KO:K04850]
101418484  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
101421427  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
101431251  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
101442429  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X2 [KO:K04515] [EC:2.7.11.17]
101445683  CAMK2B; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
101438745  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
101427403  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101436114  KCNMA1; calcium-activated potassium channel subunit alpha-1 [KO:K04936]
101431615  KCNU1; potassium channel subfamily U member 1 [KO:K05274]
101430662  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
101435149  KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
101444737  KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X1 [KO:K04939]
101438404  KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
101431308  KCNN2; small conductance calcium-activated potassium channel protein 2 [KO:K04943]
101426233  KCNN3; small conductance calcium-activated potassium channel protein 3 isoform X1 [KO:K04944]
101412660  KCNN4; intermediate conductance calcium-activated potassium channel protein 4 isoform X1 [KO:K04945]
101417326  GCG; glucagon isoform X1 [KO:K05259]
101440576  GLP1R; glucagon-like peptide 1 receptor [KO:K04581]
101429453  GIP; gastric inhibitory polypeptide [KO:K05258]
101432404  GPR119; glucose-dependent insulinotropic receptor [KO:K08424]
101444293  ADCYAP1; pituitary adenylate cyclase-activating polypeptide [KO:K05262]
101437293  ADCYAP1R1; pituitary adenylate cyclase-activating polypeptide type I receptor isoform X1 [KO:K04587]
101428152  neuroendocrine secretory protein 55-like [KO:K04632]
101411559  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101411573  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101419332  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101417345  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101442950  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101427927  ADCY7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101422732  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
101442901  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101413809  cAMP-dependent protein kinase type 2 [KO:K04345] [EC:2.7.11.11]
101423692  PRKACB; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101445596  uncharacterized protein LOC101445596 [KO:K04345] [EC:2.7.11.11]
101434860  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
101414225  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101410933  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101410879  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
101414637  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101424631  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101411890  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101435604  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101442310  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101426399  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
101425452  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
101432986  PDX1; pancreas/duodenum homeobox protein 1 [KO:K07594]
101440135  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
101419769  RIMS2; regulating synaptic membrane exocytosis protein 2 isoform X11 [KO:K15297]
101425326  PCLO; LOW QUALITY PROTEIN: protein piccolo [KO:K16882]
101434642  RAB3A; ras-related protein Rab-3A [KO:K07882]
101423015  CCK; cholecystokinin [KO:K05226]
101411254  CCKAR; cholecystokinin receptor type A [KO:K04194]
101434986  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
101447609  FFAR1; LOW QUALITY PROTEIN: free fatty acid receptor 1 [KO:K04325]
111765858  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
101411610  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101420315  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101419878  PLCB4; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
101413654  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
101427179  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:3.1.4.11]
101425999  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101430953  VAMP2; vesicle-associated membrane protein 2 [KO:K13504]
101421898  STX1A; LOW QUALITY PROTEIN: syntaxin-1A [KO:K04560]
101411616  SNAP25; synaptosomal-associated protein 25 isoform X1 [KO:K18211]
101447838  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101421680  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101447351  PRKCG; protein kinase C gamma type isoform X1 [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
PMID:20551594
  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
PMID:20225132
  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
PMID:22974438
  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
PMID:21934040
  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
PMID:10605628
  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
PMID:19036624
  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
PMID:15655710
  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
PMID:15271645
  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
PMID:17306374
  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
PMID:19074620
  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
PMID:19817800
  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
PMID:22970724
  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
PMID:14693691
  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
PMID:20055708
  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
PMID:17084085
  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
PMID:11522660
  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
PMID:19817784
  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
PMID:19660440
  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
dnm00020  Citrate cycle (TCA cycle)
dnm04020  Calcium signaling pathway
KO pathway
ko04911   
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