Entry |
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Name |
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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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Disease |
H00409 | Type 2 diabetes mellitus |
H01947 | Fanconi-Bickel syndrome |
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Other DBs |
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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 |
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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. |
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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. |
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Reference |
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Authors |
Rorsman P, Braun M |
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Regulation of insulin secretion in human pancreatic islets. |
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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. |
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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. |
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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. |
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Reference |
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Authors |
Kieffer TJ, Habener JF |
Title |
The glucagon-like peptides. |
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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. |
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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. |
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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. |
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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. |
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Reference |
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Authors |
Bos JL |
Title |
Epac proteins: multi-purpose cAMP targets. |
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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. |
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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? |
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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. |
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Related pathway |
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LinkDB |
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