A computational systems analysis of factors regulating α cell glucagon secretion
Glucagon, a peptide hormone secreted from the α-cells of the pancreatic islets, is critical for blood glucose homeostasis. We reviewed the literature and employed a computational systems analysis of intracellular metabolic and electrical regulation of glucagon secretion to better understand these pr...
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| Veröffentlicht in: | Islets 2012-07, Vol.4 (4), p.262-283 |
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| creator | Fridlyand, Leonid E. Philipson, Louis H. |
| description | Glucagon, a peptide hormone secreted from the α-cells of the pancreatic islets, is critical for blood glucose homeostasis. We reviewed the literature and employed a computational systems analysis of intracellular metabolic and electrical regulation of glucagon secretion to better understand these processes. The mathematical model of α-cell metabolic parameters is based on our previous model for pancreatic β-cells. We also formulated an ionic model for action potentials that incorporates Ca
2+
, K
+
, Na
+
and Cl
-
currents. Metabolic and ionic models are coupled to the equations describing Ca
2+
homeostasis and glucagon secretion that depends on activation of specific voltage-gated Ca
2+
channels. Paracrine and endocrine regulations were analyzed with an emphasis on their effects on a hyperpolarization of membrane potential. This general model simulates and gives insight into the mechanisms of regulation of glucagon secretion under a wide range of experimental conditions. We also reviewed and analyzed dysfunctional mechanisms in α-cells to determine key pharmacological targets for modulating glucagon secretion in type 1 and 2 diabetes. |
| doi_str_mv | 10.4161/isl.22193 |
| format | Article |
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2+
, K
+
, Na
+
and Cl
-
currents. Metabolic and ionic models are coupled to the equations describing Ca
2+
homeostasis and glucagon secretion that depends on activation of specific voltage-gated Ca
2+
channels. Paracrine and endocrine regulations were analyzed with an emphasis on their effects on a hyperpolarization of membrane potential. This general model simulates and gives insight into the mechanisms of regulation of glucagon secretion under a wide range of experimental conditions. We also reviewed and analyzed dysfunctional mechanisms in α-cells to determine key pharmacological targets for modulating glucagon secretion in type 1 and 2 diabetes.</description><identifier>ISSN: 1938-2014</identifier><identifier>EISSN: 1938-2022</identifier><identifier>DOI: 10.4161/isl.22193</identifier><identifier>PMID: 23093806</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Binding ; Biological Transport ; Biology ; Bioscience ; Calcium ; Calcium - metabolism ; Calcium Channels - physiology ; Cancer ; Cell ; Chloride Channels - physiology ; computational model ; Computer Simulation ; Cycle ; diabetes ; Diabetes Mellitus - metabolism ; Diabetes Mellitus - physiopathology ; Electrophysiological Phenomena ; Glucagon - antagonists & inhibitors ; Glucagon - secretion ; Glucagon-Secreting Cells - physiology ; Glucagon-Secreting Cells - secretion ; Glucose - metabolism ; Glucose - pharmacokinetics ; Hormones - metabolism ; Humans ; insulin ; ion channels ; islets ; Landes ; Membrane Potentials ; Models, Biological ; Organogenesis ; pancreas ; Paracrine Communication ; Potassium Channels - physiology ; Proteins ; Review ; Systems Biology</subject><ispartof>Islets, 2012-07, Vol.4 (4), p.262-283</ispartof><rights>Copyright © 2012 Landes Bioscience 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-84594ea20a36c0849276fcc91cebfb51f1b5e221fa2b10449ff655da974e28373</citedby><cites>FETCH-LOGICAL-c509t-84594ea20a36c0849276fcc91cebfb51f1b5e221fa2b10449ff655da974e28373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496652/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496652/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23093806$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fridlyand, Leonid E.</creatorcontrib><creatorcontrib>Philipson, Louis H.</creatorcontrib><title>A computational systems analysis of factors regulating α cell glucagon secretion</title><title>Islets</title><addtitle>Islets</addtitle><description>Glucagon, a peptide hormone secreted from the α-cells of the pancreatic islets, is critical for blood glucose homeostasis. We reviewed the literature and employed a computational systems analysis of intracellular metabolic and electrical regulation of glucagon secretion to better understand these processes. The mathematical model of α-cell metabolic parameters is based on our previous model for pancreatic β-cells. We also formulated an ionic model for action potentials that incorporates Ca
2+
, K
+
, Na
+
and Cl
-
currents. Metabolic and ionic models are coupled to the equations describing Ca
2+
homeostasis and glucagon secretion that depends on activation of specific voltage-gated Ca
2+
channels. Paracrine and endocrine regulations were analyzed with an emphasis on their effects on a hyperpolarization of membrane potential. This general model simulates and gives insight into the mechanisms of regulation of glucagon secretion under a wide range of experimental conditions. We also reviewed and analyzed dysfunctional mechanisms in α-cells to determine key pharmacological targets for modulating glucagon secretion in type 1 and 2 diabetes.</description><subject>Animals</subject><subject>Binding</subject><subject>Biological Transport</subject><subject>Biology</subject><subject>Bioscience</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Calcium Channels - physiology</subject><subject>Cancer</subject><subject>Cell</subject><subject>Chloride Channels - physiology</subject><subject>computational model</subject><subject>Computer Simulation</subject><subject>Cycle</subject><subject>diabetes</subject><subject>Diabetes Mellitus - metabolism</subject><subject>Diabetes Mellitus - physiopathology</subject><subject>Electrophysiological Phenomena</subject><subject>Glucagon - antagonists & inhibitors</subject><subject>Glucagon - secretion</subject><subject>Glucagon-Secreting Cells - physiology</subject><subject>Glucagon-Secreting Cells - secretion</subject><subject>Glucose - metabolism</subject><subject>Glucose - pharmacokinetics</subject><subject>Hormones - metabolism</subject><subject>Humans</subject><subject>insulin</subject><subject>ion channels</subject><subject>islets</subject><subject>Landes</subject><subject>Membrane Potentials</subject><subject>Models, Biological</subject><subject>Organogenesis</subject><subject>pancreas</subject><subject>Paracrine Communication</subject><subject>Potassium Channels - physiology</subject><subject>Proteins</subject><subject>Review</subject><subject>Systems Biology</subject><issn>1938-2014</issn><issn>1938-2022</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><recordid>eNqFkUtuFDEQhi1ERB6w4ALIWxYTbLe7Z7xBiqIAkUZCebC2qt3lxshtj2wPaI7FRTgTTiY0RCyyKZdVf32l-ouQ15ydSt7xdy77UyG4ap6RoxpXC8GEeD7nXB6S45y_MdYpweQLcigaVkusOyJXZ9TEabMtUFwM4Gne5YJTplA_u-wyjZZaMCWmTBOOW1-FYaS_flKD3tPRbw2MMdCMJuEd4yU5sOAzvnp4T8iXDxe3558W688fL8_P1gvTMlUWK9kqiSAYNJ1hK6nEsrPGKG6wt33LLe9brEtZED1nUipru7YdQC0lilWzbE7I-z13s-0nHAyGksDrTXITpJ2O4PTjSnBf9Ri_60aqrmtFBbzdA0yKOSe0cy9n-s5XXX3V975W7Zt_h83KP0ZWgdwLPIQBc-9iNg6DwVlaYViyhlSc8Thzmyfa6vnE5c364vaG1aNe681g_w5zwcY0wY-Y_KAL7HxMNkEwLuvm_yV-A9mRrew</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Fridlyand, Leonid E.</creator><creator>Philipson, Louis H.</creator><general>Taylor & Francis</general><general>Landes Bioscience</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20120701</creationdate><title>A computational systems analysis of factors regulating α cell glucagon secretion</title><author>Fridlyand, Leonid E. ; Philipson, Louis H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-84594ea20a36c0849276fcc91cebfb51f1b5e221fa2b10449ff655da974e28373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Binding</topic><topic>Biological Transport</topic><topic>Biology</topic><topic>Bioscience</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Calcium Channels - physiology</topic><topic>Cancer</topic><topic>Cell</topic><topic>Chloride Channels - physiology</topic><topic>computational model</topic><topic>Computer Simulation</topic><topic>Cycle</topic><topic>diabetes</topic><topic>Diabetes Mellitus - metabolism</topic><topic>Diabetes Mellitus - physiopathology</topic><topic>Electrophysiological Phenomena</topic><topic>Glucagon - antagonists & inhibitors</topic><topic>Glucagon - secretion</topic><topic>Glucagon-Secreting Cells - physiology</topic><topic>Glucagon-Secreting Cells - secretion</topic><topic>Glucose - metabolism</topic><topic>Glucose - pharmacokinetics</topic><topic>Hormones - metabolism</topic><topic>Humans</topic><topic>insulin</topic><topic>ion channels</topic><topic>islets</topic><topic>Landes</topic><topic>Membrane Potentials</topic><topic>Models, Biological</topic><topic>Organogenesis</topic><topic>pancreas</topic><topic>Paracrine Communication</topic><topic>Potassium Channels - physiology</topic><topic>Proteins</topic><topic>Review</topic><topic>Systems Biology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fridlyand, Leonid E.</creatorcontrib><creatorcontrib>Philipson, Louis H.</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Islets</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fridlyand, Leonid E.</au><au>Philipson, Louis H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A computational systems analysis of factors regulating α cell glucagon secretion</atitle><jtitle>Islets</jtitle><addtitle>Islets</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>4</volume><issue>4</issue><spage>262</spage><epage>283</epage><pages>262-283</pages><issn>1938-2014</issn><eissn>1938-2022</eissn><abstract>Glucagon, a peptide hormone secreted from the α-cells of the pancreatic islets, is critical for blood glucose homeostasis. We reviewed the literature and employed a computational systems analysis of intracellular metabolic and electrical regulation of glucagon secretion to better understand these processes. The mathematical model of α-cell metabolic parameters is based on our previous model for pancreatic β-cells. We also formulated an ionic model for action potentials that incorporates Ca
2+
, K
+
, Na
+
and Cl
-
currents. Metabolic and ionic models are coupled to the equations describing Ca
2+
homeostasis and glucagon secretion that depends on activation of specific voltage-gated Ca
2+
channels. Paracrine and endocrine regulations were analyzed with an emphasis on their effects on a hyperpolarization of membrane potential. This general model simulates and gives insight into the mechanisms of regulation of glucagon secretion under a wide range of experimental conditions. We also reviewed and analyzed dysfunctional mechanisms in α-cells to determine key pharmacological targets for modulating glucagon secretion in type 1 and 2 diabetes.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>23093806</pmid><doi>10.4161/isl.22193</doi><tpages>22</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Binding Biological Transport Biology Bioscience Calcium Calcium - metabolism Calcium Channels - physiology Cancer Cell Chloride Channels - physiology computational model Computer Simulation Cycle diabetes Diabetes Mellitus - metabolism Diabetes Mellitus - physiopathology Electrophysiological Phenomena Glucagon - antagonists & inhibitors Glucagon - secretion Glucagon-Secreting Cells - physiology Glucagon-Secreting Cells - secretion Glucose - metabolism Glucose - pharmacokinetics Hormones - metabolism Humans insulin ion channels islets Landes Membrane Potentials Models, Biological Organogenesis pancreas Paracrine Communication Potassium Channels - physiology Proteins Review Systems Biology |
| title | A computational systems analysis of factors regulating α cell glucagon secretion |
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