Entry Name Insulin secretion - Equus przewalskii (Przewalski's horse)
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 systemBRITE hierarchy
Pathway map Other DBs Organism Equus przewalskii (Przewalski's horse) [GN:
epz ]
Gene 103540740 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
103542504 KCNN1; small conductance calcium-activated potassium channel protein 1 isoform X1 [KO:K04942 ]
103543382 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
103543801 ABCC8; ATP-binding cassette sub-family C member 8 isoform X1 [KO:K05032 ]
103543955 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
103545804 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
103545814 KCNJ11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004 ]
103546363 SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593 ]
103546976 KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X2 [KO:K04943 ]
103548764 FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X7 [KO:K01538 ]
103548908 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
103549121 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
103549465 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
103549491 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X11 [KO:K09047 ]
103549616 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
103550311 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X6 [KO:K04936 ]
103550899 KCNN4; intermediate conductance calcium-activated potassium channel protein 4 isoform X1 [KO:K04945 ]
103551192 CHRM3; muscarinic acetylcholine receptor M3 isoform X1 [KO:K04131 ]
103551776 SNAP25; synaptosomal-associated protein 25 isoform X1 [KO:K18211 ]
103552452 RIMS2; regulating synaptic membrane exocytosis protein 2 isoform X41 [KO:K15297 ]
103552562 KCNMB2; calcium-activated potassium channel subunit beta-2 isoform X2 [KO:K04938 ]
103552869 KCNN3; small conductance calcium-activated potassium channel protein 3 isoform X1 [KO:K04944 ]
103553333 TRPM4; transient receptor potential cation channel subfamily M member 4 isoform X1 [KO:K04979 ]
103553450 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
103553756 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
103554952 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
103555399 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048 ]
103557126 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
103557406 KCNMB4; calcium-activated potassium channel subunit beta-4 isoform X1 [KO:K04941 ]
103557709 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540 ]
103559362 ADCYAP1R1; pituitary adenylate cyclase-activating polypeptide type I receptor isoform X1 [KO:K04587 ]
103559592 RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
103559733 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
103560297 CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
103560615 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
103560754 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
103561633 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
103562440 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
103563075 ADCYAP1; pituitary adenylate cyclase-activating polypeptide [KO:K05262 ]
103563236 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
103563297 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
103563810 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
103564266 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
103564286 VAMP2; vesicle-associated membrane protein 2 isoform X1 [KO:K13504 ]
103564724 ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1 [KO:K04960 ]
103565109 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
103565289 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
103566499 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Seino S, Shibasaki T, Minami K
Title Pancreatic beta-cell signaling: toward better understanding of diabetes and its treatment.
Journal Reference Authors Jitrapakdee S, Wutthisathapornchai A, Wallace JC, MacDonald MJ
Title Regulation of insulin secretion: role of mitochondrial signalling.
Journal Reference Authors Rorsman P, Braun M
Title Regulation of insulin secretion in human pancreatic islets.
Journal Reference Authors Jones PM, Persaud SJ
Title Protein kinases, protein phosphorylation, and the regulation of insulin secretion from pancreatic beta-cells.
Journal Reference Authors MacDonald PE
Title Signal integration at the level of ion channel and exocytotic function in pancreatic beta-cells.
Journal Reference Authors Lang J
Title Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion.
Journal Reference Authors Kieffer TJ, Habener JF
Title The glucagon-like peptides.
Journal 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 Reference Authors Holz GG
Title New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells.
Journal Reference Authors Holst JJ, Gromada J
Title Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans.
Journal Reference Authors Doyle ME, Egan JM
Title Mechanisms of action of glucagon-like peptide 1 in the pancreas.
Journal Reference Authors Kim W, Egan JM
Title The role of incretins in glucose homeostasis and diabetes treatment.
Journal Reference Authors Seino S, Takahashi H, Fujimoto W, Shibasaki T
Title Roles of cAMP signalling in insulin granule exocytosis.
Journal Reference Authors Tengholm A
Title Cyclic AMP dynamics in the pancreatic beta-cell.
Journal 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 Reference Authors Gloerich M, Bos JL
Title Epac: defining a new mechanism for cAMP action.
Journal Reference Authors Bos JL
Title Epac proteins: multi-purpose cAMP targets.
Journal Reference Authors Filipsson K, Kvist-Reimer M, Ahren B
Title The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet function.
Journal Reference Authors Kebede MA, Alquier T, Latour MG, Poitout V
Title Lipid receptors and islet function: therapeutic implications?
Journal Reference Authors Morgan NG, Dhayal S
Title G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell.
Journal Related KO pathway
