Entry |
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Name |
Insulin secretion - Rousettus aegyptiacus (Egyptian rousette)
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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.
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Class |
Organismal Systems; Endocrine system
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Pathway map |

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Other DBs |
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Organism |
Rousettus aegyptiacus (Egyptian rousette) [GN: ray]
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Gene |
107508288 | SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299] |
107501411 | SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593] |
107498826 | TRPM4; transient receptor potential cation channel subfamily M member 4 isoform X1 [KO:K04979] |
107509410 | ATP1B3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540] |
107512755 | ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540] |
107515690 | ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540] |
107505043 | FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538] |
107508030 | ABCC8; ATP-binding cassette sub-family C member 8 isoform X1 [KO:K05032] |
107508032 | KCNJ11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004] |
107500540 | CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850] |
107516535 | CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851] |
107514999 | CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853] |
107513628 | CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857] |
107510894 | CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17] |
107512385 | CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17] |
107497167 | CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17] |
107498266 | CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17] |
107518064 | KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936] |
107515946 | KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274] |
107518473 | KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937] |
107517571 | KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938] |
107518045 | KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X1 [KO:K04939] |
107514514 | KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941] |
107521731 | KCNN1; small conductance calcium-activated potassium channel protein 1 isoform X1 [KO:K04942] |
107512127 | KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X1 [KO:K04943] |
107504719 | KCNN3; small conductance calcium-activated potassium channel protein 3 isoform X1 [KO:K04944] |
107512308 | KCNN4; intermediate conductance calcium-activated potassium channel protein 4 isoform X1 [KO:K04945] |
107515469 | GLP1R; LOW QUALITY PROTEIN: glucagon-like peptide 1 receptor [KO:K04581] |
107520585 | ADCYAP1; pituitary adenylate cyclase-activating polypeptide isoform X1 [KO:K05262] |
107499553 | ADCYAP1R1; pituitary adenylate cyclase-activating polypeptide type I receptor isoform X1 [KO:K04587] |
107500067 | GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632] |
107505169 | CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870] |
107504977 | ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450] |
107500816 | ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374] |
107509179 | CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048] |
107502779 | CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048] |
107511864 | CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048] |
107510647 | CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048] |
107499057 | CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048] |
107505683 | CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047] |
107498439 | ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049] |
107505164 | RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351] |
107512205 | RIMS2; regulating synaptic membrane exocytosis protein 2 isoform X1 [KO:K15297] |
107517194 | GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634] |
107520124 | GNA11; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit alpha-11 [KO:K04635] |
107506114 | PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107519930 | PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107497081 | PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107514464 | PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107511965 | ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960] |
107515669 | VAMP2; vesicle-associated membrane protein 2 isoform X1 [KO:K13504] |
107507100 | SNAP25; synaptosomal-associated protein 25 isoform X1 [KO:K18211] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
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Reference |
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Authors |
Seino S, Shibasaki T, Minami K |
Title |
Pancreatic beta-cell signaling: toward better understanding of diabetes and its treatment. |
Journal |
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Reference |
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Authors |
Jitrapakdee S, Wutthisathapornchai A, Wallace JC, MacDonald MJ |
Title |
Regulation of insulin secretion: role of mitochondrial signalling. |
Journal |
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Reference |
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Authors |
Rorsman P, Braun M |
Title |
Regulation of insulin secretion in human pancreatic islets. |
Journal |
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Reference |
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Authors |
Jones PM, Persaud SJ |
Title |
Protein kinases, protein phosphorylation, and the regulation of insulin secretion from pancreatic beta-cells. |
Journal |
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Reference |
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Authors |
MacDonald PE |
Title |
Signal integration at the level of ion channel and exocytotic function in pancreatic beta-cells. |
Journal |
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Reference |
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Authors |
Lang J |
Title |
Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. |
Journal |
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Reference |
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Authors |
Kieffer TJ, Habener JF |
Title |
The glucagon-like peptides. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Holz GG |
Title |
New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells. |
Journal |
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Reference |
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Authors |
Holst JJ, Gromada J |
Title |
Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. |
Journal |
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Reference |
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Authors |
Doyle ME, Egan JM |
Title |
Mechanisms of action of glucagon-like peptide 1 in the pancreas. |
Journal |
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Reference |
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Authors |
Kim W, Egan JM |
Title |
The role of incretins in glucose homeostasis and diabetes treatment. |
Journal |
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Reference |
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Authors |
Seino S, Takahashi H, Fujimoto W, Shibasaki T |
Title |
Roles of cAMP signalling in insulin granule exocytosis. |
Journal |
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Reference |
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Authors |
Tengholm A |
Title |
Cyclic AMP dynamics in the pancreatic beta-cell. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Gloerich M, Bos JL |
Title |
Epac: defining a new mechanism for cAMP action. |
Journal |
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Reference |
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Authors |
Bos JL |
Title |
Epac proteins: multi-purpose cAMP targets. |
Journal |
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Reference |
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Authors |
Filipsson K, Kvist-Reimer M, Ahren B |
Title |
The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet function. |
Journal |
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Reference |
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Authors |
Kebede MA, Alquier T, Latour MG, Poitout V |
Title |
Lipid receptors and islet function: therapeutic implications? |
Journal |
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Reference |
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Authors |
Morgan NG, Dhayal S |
Title |
G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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