113247PathwayPancreas Function - Delta CellPancreatic delta cells produce somatostatin which functions to inhibit glucagon, insulin, and itself. Somatostatin is stored in granules in the delta cell and is released in response to an increase in blood sugar, calcium, and blood amino acids during absorption of a meal. In the process of somatostatin secretion, glucose must first undergo glycolysis in the mitochondrion to increase ATP in the cell. The inside of the alpha cell then becomes electrically positive due to the closure of potassium channels that were inhibited by ATP. From this closure, the potassium is no longer being shuttled out of the cell, thus depolarizing the cell due to the extra intracellular potassium. The resulting action potential from the increased membrane potential causes the voltage gate calcium channels to open, creating an influx of calcium into the cell. This triggers the exocytosis of somatostatin granules from the delta cell. PhysiologicalPW122406CenterPathwayVisualizationContext12268313503250#000099PathwayVisualization113110113247Pancreas Function - Delta CellPancreatic delta cells produce somatostatin which functions to inhibit glucagon, insulin, and itself. Somatostatin is stored in granules in the delta cell and is released in response to an increase in blood sugar, calcium, and blood amino acids during absorption of a meal. In the process of somatostatin secretion, glucose must first undergo glycolysis in the mitochondrion to increase ATP in the cell. The inside of the alpha cell then becomes electrically positive due to the closure of potassium channels that were inhibited by ATP. From this closure, the potassium is no longer being shuttled out of the cell, thus depolarizing the cell due to the extra intracellular potassium. The resulting action potential from the increased membrane potential causes the voltage gate calcium channels to open, creating an influx of calcium into the cell. This triggers the exocytosis of somatostatin granules from the delta cell. Physiological111001576SubPathway10959377Compound66109594414Compound66110016ATP Inhibition of ABCC8InhibitorySubPathway109595414Compound66109596750ProteinComplex66110017DepolarizationSubPathway27992426216135Brereton MF, Vergari E, Zhang Q, Clark A: Alpha-, Delta- and PP-cells: Are They the Architectural Cornerstones of Islet Structure and Co-ordination? J Histochem Cytochem. 2015 Aug;63(8):575-91. doi: 10.1369/0022155415583535.113247Pathway27992522969729Gaisano HY, Macdonald PE, Vranic M: Glucagon secretion and signaling in the development of diabetes. Front Physiol. 2012 Sep 4;3:349. doi: 10.3389/fphys.2012.00349. eCollection 2012.113247Pathway6MyocyteCL:00001875HepatocyteCL:00001821CellCL:00000007Epithelial CellCL:00000668Beta cellCL:000063910Glial cellCL:00001253NeuronCL:00005402Platelet CL:00002334CardiomyocyteCL:00007469Pancreatic Beta CellCL:000016932Acinar CellCL:000062223T CellCL:000008426Endothelial cellCL:000011515Delta CellCL:00001731Homo sapiens9606EukaryoteHuman24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress3Escherichia coli562Prokaryote18Saccharomyces cerevisiae4932EukaryoteYeast12Mus musculus10090EukaryoteMouse23Pseudomonas aeruginosa287Prokaryote5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly6Caenorhabditis elegans6239EukaryoteRoundworm51Picea sitchensis3332EukaryoteSitka spruce2Bacteria2ProkaryoteBacteria19Schizosaccharomyces pombe4896Eukaryote21Xenopus laevis8355EukaryoteAfrican clawed frog25Escherichia coli (strain K12)83333Prokaryote49Bathymodiolus platifrons220390EukaryoteDeep sea mussel60Nitzschia sp.0001EukaryoteNitzschia462Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)62977Prokaryote333Elephantidae9780EukaryoteElephant157Acinetobacter baumannii 107673Prokaryote5CytoplasmGO:00057371CytosolGO:000582925Golgi ApparatusGO:00057946LysosomeGO:00057643Mitochondrial MatrixGO:000575911Extracellular SpaceGO:00056152MitochondrionGO:000573931Periplasmic SpaceGO:000562035ChloroplastGO:000950710Cell MembraneGO:000588619Sarcoplasmic ReticulumGO:00165297Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575814Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:000578316Lysosomal LumenGO:004320236MembraneGO:001602015NucleusGO:00056344PeroxisomeGO:000577727Peroxisome MembraneGO:000577832Inner MembraneGO:007025830Lysosomal MembraneGO:000576538Apical cell membraneGO:001632422post-synaptic membraneGO:004521165Presynaptic membraneGO:004273433Outer MembraneGO:004316548Cell cortexGO:00059389MuscleBTO:0000887141181LiverBTO:00007597298Blood VesselBTO:0001102741125IntestineBTO:000064818PancreasBTO:00009887Nervous SystemBTO:00014843Sympathetic Nervous SystemBTO:00018326KidneyBTO:00006717182Endothelium BTO:00003935cardiocyteBTO:000153911HeartBTO:0000562731028StomachBTO:00013071552624BrainBTO:0000142891626LungBTO:000076314EyeBTO:00004391532422BladderBTO:000012348Salivary GlandBTO:000120338Myenteric PlexusBTO:000243647Spinal 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is a monosaccharide containing six carbon atoms and an aldehyde group and is therefore referred to as an aldohexose. The glucose molecule can exist in an open-chain (acyclic) and ring (cyclic) form, the latter being the result of an intramolecular reaction between the aldehyde C atom and the C-5 hydroxyl group to form an intramolecular hemiacetal. In water solution both forms are in equilibrium and at pH 7 the cyclic one is the predominant. Glucose is a primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. In animals glucose arises from the breakdown of glycogen in a process known as glycogenolysis. Glucose is synthesized in the liver and kidneys from non-carbohydrate intermediates, such as pyruvate and glycerol, by a process known as gluconeogenesis.2280-44-6C0003157934167GLC5589[H]C1(O)O[C@]([H])(CO)[C@@]([H])(O)[C@]([H])(O)[C@@]1([H])OC6H12O6InChI=1S/C6H12O6/c7-1-2-3(8)4(9)5(10)6(11)12-2/h2-11H,1H2/t2-,3-,4+,5-,6?/m1/s1WQZGKKKJIJFFOK-GASJEMHNSA-N180.1559180.063388116FDB012530Roferose st;(+)-glucose;Anhydrous dextrose;Cpc hydrate;Cerelose;Cerelose 2001;Clearsweet 95;Clintose l;Corn sugar;D(+)-glucose;Dextropur;Dextrose;Dextrosol;Glucodin;Glucolin;Glucose;Goldsugar;Grape sugar;Meritose;Staleydex 111;Staleydex 95m;Tabfine 097(hs);Vadex;D-glc;D-glcp;D-glucosePW_C000077D-Glc1452501460261461511506215404321939243942679602721152723613027663114293593356926589614859221495923152595415363671076368108686919269041937085200724421511765114117661324244031842441315770853267711732777923336779893467823635278248353782623567888111379056112121166424121167416121169423121251429121361124121373419122098126122385436122388437122399407122676409123738459123739452123741458123821464123920118123932455124649443124939471124959472124969119125251137125937488125967492126034299126046490126254301126540481126809483127397505127423509127486388127498507127817207128113206128408208457PotassiumHMDB0000586Potassium is an essential electrolyte. Potassium balance is crucial for regulating the excitability of nerves and muscles and so critical for regulating contractility of cardiac muscle. Although the most important changes seen in the presence of deranged potassium are cardiac, smooth muscle is also affected with increasing muscle weakness, a feature of both hyperkalaemia and hypokalaemia. Physiologically, it exists as an ion in the body. Potassium (K+) is a positively charged electrolyte, cation, which is present throughout the body in both intracellular and extracellular fluids. The majority of body potassium, >90%, are intracellular. It moves freely from intracellular fluid (ICF) to extracellular fluid (ECF) and vice versa when adenosine triphosphate increases the permeability of the cell membrane. It is mainly replaced inside or outside the cells by another cation, sodium (Na+). The movement of potassium into or out of the cells is linked to certain body hormones and also to certain physiological states. Standard laboratory tests measure ECF potassium. Potassium enters the body rapidly during food ingestion. Insulin is produced when a meal is eaten; this causes the temporary movement of potassium from ECF to ICF. Over the ensuing hours, the kidneys excrete the ingested potassium and homeostasis is returned. In the critically ill patient, suffering from hyperkalaemia, this mechanism can be manipulated beneficially by administering high concentration (50%) intravenous glucose. Insulin can be added to the glucose, but glucose alone will stimulate insulin production and cause movement of potassium from ECF to ICF. The stimulation of alpha receptors causes increased movement of potassium from ICF to ECF. A noradrenaline infusion can elevate serum potassium levels. An adrenaline infusion, or elevated adrenaline levels, can lower serum potassium levels. Metabolic acidosis causes a rise in extracellular potassium levels. In this situation, excess of hydrogen ions (H+) are exchanged for intracellular potassium ions, probably as a result of the cellular response to a falling blood pH. Metabolic alkalosis causes the opposite effect, with potassium moving into the cells. (PMID: 17883675).24203-36-9C0023881329103K%2b791DB01345[K+]KInChI=1S/K/q+1NPYPAHLBTDXSSS-UHFFFAOYSA-N39.098338.963706861FDB003521K+;Kalium;Potassium;Potassium (k+);Potassium (ion);Potassium cation;Potassium ion;Potassium ion (k+);Potassium ion (k1+);Potassium ion(+);Potassium ion(1+);Potassium monocation;Potassium(+);Potassium(1+);Potassium(1+) ion;Potassium(i) cation;K(+)PW_C000457K+5738931191926220951530336631617231627136135136146159211475952151690216011810198152223067702322577115132776101117824132678246353120484122121198124123105135123768118124944452124949472125860297125965299127322205127421388140680834140681790140687781353CalciumHMDB0000464Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.14127-61-8C0007627129108CA%2b2266DB01373[Ca++]CaInChI=1S/Ca/q+2BHPQYMZQTOCNFJ-UHFFFAOYSA-N40.07839.962591155FDB003513Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ionPW_C000353Ca2+27616303855314601294115993219973510463116346116447147849149142155243211658213817279618293793159713160723942294186664782104822285340111578010171792057232211725816072811901177421311837198118422101219816412215285152881511535030869336177389331776001157815413278266356785263457872413078908114804137480589228818265112022012212046540512104912412130041812137741912185038312192312512237040912289513512309937612361311812387045412393645512440339812447613612492413712557129712571147812598148912600929912605049012653349512720320912743450612746038812750250712810539014067679014067783414069550414Adenosine triphosphateHMDB0000538Adenosine triphosphate (ATP) is a nucleotide consisting of a purine base (adenine) attached to the first carbon atom of ribose (a pentose sugar). Three phosphate groups are esterified at the fifth carbon atom of the ribose. ATP is incorporated into nucleic acids by polymerases in the processes of DNA replication and transcription. ATP contributes to cellular energy charge and participates in overall energy balance, maintaining cellular homeostasis. ATP can act as an extracellular signaling molecule via interactions with specific purinergic receptors to mediate a wide variety of processes as diverse as neurotransmission, inflammation, apoptosis, and bone remodelling. Extracellular ATP and its metabolite adenosine have also been shown to exert a variety of effects on nearly every cell type in human skin, and ATP seems to play a direct role in triggering skin inflammatory, regenerative, and fibrotic responses to mechanical injury, an indirect role in melanocyte proliferation and apoptosis, and a complex role in Langerhans cell-directed adaptive immunity. During exercise, intracellular homeostasis depends on the matching of adenosine triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in communicating the extent of ATP demand to the metabolic supply pathways. Effects as different as proliferation or differentiation, chemotaxis, release of cytokines or lysosomal constituents, and generation of reactive oxygen or nitrogen species are elicited upon stimulation of blood cells with extracellular ATP. The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. (PMID: 15490415, 15129319, 14707763, 14696970, 11157473).56-65-5C00002595715422ATP5742DB00171NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1OC10H16N5O13P3InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1ZKHQWZAMYRWXGA-KQYNXXCUSA-N507.181506.995745159FDB0218135'-(tetrahydrogen triphosphate) adenosine;5'-atp;Atp;Adenosine 5'-triphosphate;Adenosine 5'-triphosphorate;Adenosine 5'-triphosphoric acid;Adenosine triphosphate;Adenylpyrophosphorate;Adenylpyrophosphoric acid;Adephos;Adetol;Adynol;Atipi;Atriphos;Cardenosine;Fosfobion;Glucobasin;Myotriphos;Phosphobion;Striadyne;Triadenyl;Triphosphaden;Triphosphoric acid adenosine ester;Adenosine-5'-triphosphate;H4atp;Adenosine triphosphoric acid;Adenosine-5'-triphosphoric acidPW_C000414ATP922146082661641422478137333279959343997632105182112102146492156142160582405592434272726462812293029663163723616613617514399234474314768914864545032895035265155752059752151005250104529110153131115346112539010354061175430118544312055421295556132556913356031355621108584614358541465876107589714759241516048155610916162301666493178683918868701606976199715720571842067209210722521372292117298198730221673902177408218743216374812227499190818622511847277119031701201028112039164121782851257822612691290132642231532730842326315426213224269431877028253772181347723332977468333776323367803733278041350781681287821435178240353784113357849411578850130788653317891933480028368800461848067411985629194826124113234941132823881162801091199141221199924061201544071202453821203624121212464291213921231213974331214714081219744101220651251220793831220834051224024221224444351229193991230094461238164641239514471239564681240293741245274441246161361246303981246343761249434721249723751250114701253042971253714791253922991255154811255954841261234851262203001262344951262404781265474911265964991269135011271233891277315161277813951277963901278012091281195081281675171407708912449Solute carrier family 2, facilitated glucose transporter member 2P11168Facilitative glucose transporter. This isoform likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of the beta cell. May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney.
HMDBP05474SLC2A23q26.1-q26.2CH47105218451228141627531416866614193167142224308143880511439308681442729014432649144327144840ATP-binding cassette sub-family C member 8Q09428Putative subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin releaseHMDBP10762ABCC811p15.1L78223130316730766984921414023183114123545141968214240310141433121138145089522712Voltage-dependent P/Q-type calcium channel subunit alpha-1AO00555Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin- IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA)HMDBP07491CACNA1A19p13AC0987811939399423885032281363727413952945139530511397057781399054814063271406447871409973081410007314134852141932671419692142866103314287010551428981058143428114414558813671455961449145602136114564310001456491453145693111814630610141469096652720Voltage-dependent L-type calcium channel subunit beta-1Q02641The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targetingHMDBP07499CACNB117q21-q22CH47115219383927694535151435405250966580753228136133651139531511397067781398102041399064814015430814055678714058574140633714063882814100173141933671419702142397101414287210551429101058142957103314298210711434291144145144113814519413671454791409145520141414552614201455461428145565143614559714491456031361145614144414564410001456501453145873965145907116114595694514617534814626415221464551563146639159214671216091468001658146910665146931566146941167414971515342706Voltage-dependent calcium channel subunit alpha-2/delta-2Q9NY47The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosisHMDBP07485CACNA2D23p21.3AJ25136819403927684535141435395250956584992281361326511395325113970777813980920413990748140586741406243081406347140637828140643787140999731416876714197121423951014142871105514291110581429551033142980107114318911181434301144145487140914552414201455441428145563143614558913671455981449145604136114561214441456421000145651145314645615631465283481466371592146699152214671316091468011658146911665146932566146942167414971415341524SomatostatinP61278Somatostatin inhibits the release of somatotropinHMDBP01649SST3q28J003061135616813561715136158660398Solute carrier family 2, facilitated glucose transporter member 21PW_P00039842024491750ATP-binding cassette sub-family C member 81PW_P00075084548401777L type Calcium channel1PW_P000777876271218772720187827062774Somatostatin1PW_P00077487215241142PW_T000142164771Compound1566Right1043982013-09-05T10:23:21-06:002013-09-05T10:23:21-06:0067143PW_T0001431654571Compound6615Right1057502013-09-05T10:51:45-06:002013-09-05T10:51:45-06:0067210PW_T0002102453531Compound1566Right1767772013-09-17T11:07:28-06:002013-09-17T11:07:28-06:006710290PW_T010290106417741ProteinComplex815Right2840ActivationPW_I0028405679353Compound15680774ProteinComplex1268205677153false186515010regular100100268205777663false186548510regular10010026820584576657false227017510regular787826820594571557false226852510regular787826820603531551false252569510regular787826820613536651false302569510regular787826820644146642false208568010regular5030949535244922876false18403358subunitregular1507094953648401476false22333398subunitregular15070949537271222876false27506308subunitregular15070949538272076false27507708subunitregular15070949539270622876false27507008subunitregular15070949546152482false22346978subunitregular150709495471524152false223411028subunitregular150708040503981131109453669495358040517501131109453679495368040527771131109453689495379453699495389453709495398040567741131108945377949546804057774113110159453789495473665511M1915 250 C1915 275 1915 315 1915 335 83false183665512M1915 485 C1915 462 1915 423 1915 405 83false18trueM 696.9764610813569 412.32629402183323 L 705 425 L 711.9639818778655 411.7145584791186false3665513M2307 253 C2307 290 2307 290 2307 334 83false18trueM 991.8482254950279 105.78301046620838 L 984 93 L 976.8537009469352 106.18826788642711false3665514M2308 525 C2308 495 2308 478 2308 409 83false183665515M2603 734 C2633 734 2720 735 2750 735 83false18trueM 1345.9903810567666 736.5 L 1333 744 L 1345.9903810567666 751.5false3665516M3025 734 C2995 734 2930 735 2900 735 83false183665523M1915 585 C1915 615 1914 670 1914 700 5false183665524M1915 770 C1915 809 1915 863 1915 898 C1956 898 2037 899 2110 899 C2110 853 2110 764 2110 710 5false18falsefalsetrueM 2117.5 899.9903810567666 L 2110 887 L 2102.5 899.9903810567666false3665525M2110 680 C2109 645 2110 405 2109 373 C2157 373 2190 373 2222 373 148false18falsetrueM 913 274 L 913 259 L 913 2443665526M2233 374 C2203 374 959 350 929 350 5true183665527M2558 410 C2558 450 2559 647 2559 665 C2589 665 2703 665 2750 665 149false18trueM 2046.3153727401368 586.1425545792127 L 2060 580 L 2047.8380780603377 571.2200424412438false3665528M2396 376 C2417 376 2444 376 2470 376 218false18trueM 1246.6512944095607 311.8419338684158 L 1260 305 L 1247.400358663719 296.86064878524815false3665531M2309 767 C2309 797 1454 512 1454 542 83true183665532M2309 1102 C2309 1072 2309 797 2309 767 83false18trueM 1404.9468550441647 460.261556296296 L 1390 459 L 1396.380887721186 472.5751343230783false3665845M2525 734 C2495 734 2466.5 737 2436.5 737 149true183665846M2385 734 C2415 734 2495 734 2525 734 149false18trueM 1764.9468550441647 553.261556296296 L 1750 552 L 1756.380887721186 565.5751343230784false7820314211311015717726820563665511Left15717826820573665512Right247788040501047820414311311015717926820583665513Left15718026820593665514Right247798040511057820521011311015718126820603665515Left15718226820613665516Right2478080405217678208102901131107998040563665531Left8008040573665532Right77502840113110664187126820603665845Left91668040563665846Right10969211001511311014false184070016regular10636726820573665523Left10636826820643665524Right10969311001611311014true77936516regular10636926820643665525Left25968040513665526Right109694110017113110217false248334016regular686233665527686243665528186717179651902.82.8023525030018671813407731.11.1-602904844971867198255901.01.00286357309369719M1425 476 C1425 426 1475 376 1525 376 C1889 376 2362 376 2726 376 C2776 376 2826 426 2826 476 C2826 597 2826 755 2826 876 C2826 926 2776 976 2726 976 C2362 976 1889 976 1525 976 C1475 976 1425 926 1425 876 C1425 755 1425 597 1425 476 1true61401.0600.045066115Islet Cell860490201.61.61601545066215Delta Cell2152571201.91.91601545066315Exocytosis of glucagon granules from the cell2174908201.61.6160151804921028773135210131511250394179911491804934557998005021201948394401446