Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway.
Using the MIN6 B-cell line, we investigated the hypothesis that miniglucagon, the C-terminal () fragment processed from glucagon and present in pancreatic A cells, modulates insulin release, and we analyzed its cellular mode of action. We show that, at concentrations ranging from 0.01 to 1000 pM, mi...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1999
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| _version_ | 1797093645755613184 |
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| author | Dalle, S Smith, P Blache, P Le-Nguyen, D Le Brigand, L Bergeron, F Ashcroft, F Bataille, D |
| author_facet | Dalle, S Smith, P Blache, P Le-Nguyen, D Le Brigand, L Bergeron, F Ashcroft, F Bataille, D |
| author_sort | Dalle, S |
| collection | OXFORD |
| description | Using the MIN6 B-cell line, we investigated the hypothesis that miniglucagon, the C-terminal () fragment processed from glucagon and present in pancreatic A cells, modulates insulin release, and we analyzed its cellular mode of action. We show that, at concentrations ranging from 0.01 to 1000 pM, miniglucagon dose-dependently (ID50 = 1 pM) inhibited by 80-100% the insulin release triggered by glucose, glucagon, glucagon-like peptide-1-(7-36) amide (tGLP-1), or glibenclamide, but not that induced by carbachol. Miniglucagon had no significant effects on cellular cAMP levels. The increase in 45Ca2+ uptake induced by depolarizing agents (glucose or extracellular K+), by glucagon, or by the Ca2+channel agonist Bay K-8644 was blocked by miniglucagon at the doses active on insulin release. Electrophysiological experiments indicated that miniglucagon induces membrane hyperpolarization, probably by opening potassium channels, which terminated glucose-induced electrical activity. Pretreatment with pertussis toxin abolished the effects of miniglucagon on insulin release. It is concluded that miniglucagon is a highly potent and efficient inhibitor of insulin release by closing, via hyperpolarization, voltage-dependent Ca2+ channels linked to a pathway involving a pertussis toxin-sensitive G protein. |
| first_indexed | 2024-03-07T04:03:16Z |
| format | Journal article |
| id | oxford-uuid:c54eef70-3994-4894-9e2f-11debf3fd506 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:03:16Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:c54eef70-3994-4894-9e2f-11debf3fd5062022-03-27T06:29:54ZMiniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c54eef70-3994-4894-9e2f-11debf3fd506EnglishSymplectic Elements at Oxford1999Dalle, SSmith, PBlache, PLe-Nguyen, DLe Brigand, LBergeron, FAshcroft, FBataille, DUsing the MIN6 B-cell line, we investigated the hypothesis that miniglucagon, the C-terminal () fragment processed from glucagon and present in pancreatic A cells, modulates insulin release, and we analyzed its cellular mode of action. We show that, at concentrations ranging from 0.01 to 1000 pM, miniglucagon dose-dependently (ID50 = 1 pM) inhibited by 80-100% the insulin release triggered by glucose, glucagon, glucagon-like peptide-1-(7-36) amide (tGLP-1), or glibenclamide, but not that induced by carbachol. Miniglucagon had no significant effects on cellular cAMP levels. The increase in 45Ca2+ uptake induced by depolarizing agents (glucose or extracellular K+), by glucagon, or by the Ca2+channel agonist Bay K-8644 was blocked by miniglucagon at the doses active on insulin release. Electrophysiological experiments indicated that miniglucagon induces membrane hyperpolarization, probably by opening potassium channels, which terminated glucose-induced electrical activity. Pretreatment with pertussis toxin abolished the effects of miniglucagon on insulin release. It is concluded that miniglucagon is a highly potent and efficient inhibitor of insulin release by closing, via hyperpolarization, voltage-dependent Ca2+ channels linked to a pathway involving a pertussis toxin-sensitive G protein. |
| spellingShingle | Dalle, S Smith, P Blache, P Le-Nguyen, D Le Brigand, L Bergeron, F Ashcroft, F Bataille, D Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. |
| title | Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. |
| title_full | Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. |
| title_fullStr | Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. |
| title_full_unstemmed | Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. |
| title_short | Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. |
| title_sort | miniglucagon glucagon 19 29 a potent and efficient inhibitor of secretagogue induced insulin release through a ca2 pathway |
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