Entry Name Insulin secretion - Chlorocebus sabaeus (green monkey)
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 Chlorocebus sabaeus (green monkey) [GN:
csab ]
Gene 103215616 KCNU1; potassium calcium-activated channel subfamily U member 1 [KO:K05274 ]
103215949 KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936 ]
103218385 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850 ]
103221213 KCNMB3; potassium calcium-activated channel subfamily M regulatory beta subunit 3 [KO:K04939 ]
103221216 KCNMB2; potassium calcium-activated channel subfamily M regulatory beta subunit 2 [KO:K04938 ]
103223916 KCNN3; potassium calcium-activated channel subfamily N member 3 [KO:K04944 ]
103223942 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
103226974 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
103227762 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851 ]
103230339 CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857 ]
103231971 CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853 ]
103233716 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
103234161 KCNN1; potassium calcium-activated channel subfamily N member 1 [KO:K04942 ]
103234803 KCNN4; potassium calcium-activated channel subfamily N member 4 [KO:K04945 ]
103235539 TRPM4; transient receptor potential cation channel subfamily M member 4 [KO:K04979 ]
103236571 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
103238713 KCNMB4; potassium calcium-activated channel subfamily M regulatory beta subunit 4 [KO:K04941 ]
103239552 KCNJ11; potassium voltage-gated channel subfamily J member 11 [KO:K05004 ]
103244350 KCNN2; potassium calcium-activated channel subfamily N member 2 [KO:K04943 ]
103244960 KCNMB1; potassium calcium-activated channel subfamily M regulatory beta subunit 1 [KO:K04937 ]
103247357 ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540 ]
103248564 FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538 ]
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 
