Entry Name Insulin secretion
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 Ortholog table Other DBs Orthology K07299 MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K07593 MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 2
K04979 transient receptor potential cation channel subfamily M member 4
K01539 sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13 ]
K01540 sodium/potassium-transporting ATPase subunit beta
K01538 sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K05032 ATP-binding cassette subfamily C (CFTR/MRP) member 8
K05004 potassium inwardly-rectifying channel subfamily J member 11
K04850 voltage-dependent calcium channel L type alpha-1C
K04851 voltage-dependent calcium channel L type alpha-1D
K04853 voltage-dependent calcium channel L type alpha-1F
K04857 voltage-dependent calcium channel L type alpha-1S
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04936 potassium large conductance calcium-activated channel subfamily M alpha member 1
K05274 potassium large conductance calcium-activated channel subfamily M alpha member 3
K04937 potassium large conductance calcium-activated channel subfamily M beta member 1
K04938 potassium large conductance calcium-activated channel subfamily M beta member 2
K04939 potassium large conductance calcium-activated channel subfamily M beta member 3
K04941 potassium large conductance calcium-activated channel subfamily M beta member 4
K04942 potassium intermediate/small conductance calcium-activated channel subfamily N member 1
K04943 potassium intermediate/small conductance calcium-activated channel subfamily N member 2
K04944 potassium intermediate/small conductance calcium-activated channel subfamily N member 3
K04945 potassium intermediate/small conductance calcium-activated channel subfamily N member 4
K04581 glucagon-like peptide 1 receptor
K05258 gastric inhibitory polypeptide
K08424 glucose-dependent insulinotropic receptor
K05262 pituitary adenylate cyclase-activating polypeptide
K04587 pituitary adenylate cyclase-activating polypeptide type I receptor
K04632 guanine nucleotide-binding protein G(s) subunit alpha
K05870 cyclic AMP-responsive element-binding protein 1
K04450 cyclic AMP-dependent transcription factor ATF-2
K04374 cyclic AMP-dependent transcription factor ATF-4
K09048 cyclic AMP-responsive element-binding protein 3
K09047 cyclic AMP-responsive element-binding protein 5
K09049 cyclic AMP-dependent transcription factor ATF-6 beta
K07594 insulin promoter factor 1
K04351 Rap guanine nucleotide exchange factor 4
K15297 regulating synaptic membrane exocytosis protein 2
K07882 Ras-related protein Rab-3A
K04194 cholecystokinin A receptor
K04131 muscarinic acetylcholine receptor M3
K04325 free fatty acid receptor 1
K04634 guanine nucleotide-binding protein G(q) subunit alpha
K04635 guanine nucleotide-binding protein subunit alpha-11
K04960 inositol 1,4,5-triphosphate receptor type 3
K13504 vesicle-associated membrane protein 2
K18211 synaptosomal-associated protein 25
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 LinkDB All DBs
