Entry Name Insulin secretion - Peromyscus leucopus (white-footed mouse)
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 Peromyscus leucopus (white-footed mouse) [GN:
pleu ]
Gene 114680674 Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
114681679 Ffar1; LOW QUALITY PROTEIN: free fatty acid receptor 1 [KO:K04325 ]
114682227 Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
114683299 Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
114685023 Chrm3; muscarinic acetylcholine receptor M3 isoform X1 [KO:K04131 ]
114686204 Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
114687952 Kcnn1; small conductance calcium-activated potassium channel protein 1 isoform X1 [KO:K04942 ]
114688126 Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
114688160 Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
114689701 Adcyap1r1; pituitary adenylate cyclase-activating polypeptide type I receptor isoform X1 [KO:K04587 ]
114689726 Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
114689941 Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
114690908 Cckar; LOW QUALITY PROTEIN: cholecystokinin receptor type A [KO:K04194 ]
114690974 Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
114691010 Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
114693172 Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
114693978 Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X7 [KO:K04515 ] [EC:2.7.11.17 ]
114694285 Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
114695332 Kcnmb2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
114695336 Kcnmb3; calcium-activated potassium channel subunit beta-3 [KO:K04939 ]
114696421 Adcyap1; pituitary adenylate cyclase-activating polypeptide isoform X1 [KO:K05262 ]
114697557 Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593 ]
114699033 Kcnmb4; calcium-activated potassium channel subunit beta-4 isoform X1 [KO:K04941 ]
114699702 Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
114699915 Rims2; regulating synaptic membrane exocytosis protein 2 isoform X19 [KO:K15297 ]
114700183 Kcnma1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
114700207 Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
114700534 Abcc8; ATP-binding cassette sub-family C member 8 isoform X1 [KO:K05032 ]
114700535 Kcnj11; ATP-sensitive inward rectifier potassium channel 11 isoform X1 [KO:K05004 ]
114700762 Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850 ]
114700827 Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
114701281 Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
114703207 Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
114703662 Snap25; synaptosomal-associated protein 25 isoform X1 [KO:K18211 ]
114703666 Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
114703672 Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
114704477 Rapgef4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
114704945 Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299 ]
114705057 Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
114705847 Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
114707396 Camk2a; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515 ] [EC:2.7.11.17 ]
114707907 Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
114707955 Kcnn3; small conductance calcium-activated potassium channel protein 3 isoform X1 [KO:K04944 ]
114709889 Kcnn4; intermediate conductance calcium-activated potassium channel protein 4 [KO:K04945 ]
114710065 Kcnn2; small conductance calcium-activated potassium channel protein 2 isoform X1 [KO:K04943 ]
114710651 Kcnmb1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
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
