{"id":{"repo_id":"goteborg","oai_identifier":"oai:gupea.ub.gu.se:2077/64544"},"canonical_url":"https://search.dev.ndltd.org/etd/goteborg/oai:gupea.ub.gu.se:2077/64544","repository":{"repo_id":"goteborg","name":"Gothenburg University","base_url":"https://gupea.ub.gu.se/oai/request"},"display":{"title":"Paracrine control of glucagon secretion in the pancreatic α-cell: Studies involving optogenetic cell activation","abstract":"ABSTRACT The mechanisms controlling glucagon secretion by α-cells in islets of Langerhans were studied. We generated mice with the light-activated ion channel ChR2 specifically expressed in β-, α-, and δ-cells, and explored the spatio-temporal relationship between cell activation and glucagon release. In paper I, ChR2 was expressed in β-cells and photoactivation of these cells rapidly depolarized neighbouring δ-cell but produced a more delayed effect on α-cells. We showed that these effects were mediated via electrical signalling from the β- to δ-cells via gapjunction. Once activated, the δ-cells released somatostatin which repolarized the αcells following its intercellular diffusion from the δ- to the α-cells. In paper II we used a novel antibody for detection of somatostatin, which showed great efficiency compared with commercially available antibodies. Immunostaining of intact islets showed an islet-wide network involving α- and δ-cells. Furthermore, we used immunostaining to compare the islet architecture as pertaining to δ-cell number, and morphology between islets from healthy human donors and type 2 diabetic donors and found that the number of δ-cells in type 2 diabetic islets is reduced. In paper III we expressed ChR2 in α- and δ-cells in two novel mouse models. We showed that photoactivation of α-cells depolarized the α-cells and evoked action potential firing, effects that were associated with stimulation of glucagon secretion regardless of the glucose concentration. In islets exposed to 1 mM glucose, photoactivation of δ-cells transiently hyperpolarized α-cells, produced a long-lasting inhibition of glucagon exocytosis and inhibited glucagon secretion at 1 mM glucose but had no additional inhibitory effect at 6 or 20 mM glucose. The effect of somatostatin was so strong that it was possible to suppress glucagon secretion by photoactivation of δ-cells even when measurements were performed using the perfused mouse pancreas.","abstract_html":"ABSTRACT The mechanisms controlling glucagon secretion by α-cells in islets of Langerhans were studied. We generated mice with the light-activated ion channel ChR2 specifically expressed in β-, α-, and δ-cells, and explored the spatio-temporal relationship between cell activation and glucagon release. In paper I, ChR2 was expressed in β-cells and photoactivation of these cells rapidly depolarized neighbouring δ-cell but produced a more delayed effect on α-cells. We showed that these effects were mediated via electrical signalling from the β- to δ-cells via gapjunction. Once activated, the δ-cells released somatostatin which repolarized the αcells following its intercellular diffusion from the δ- to the α-cells. In paper II we used a novel antibody for detection of somatostatin, which showed great efficiency compared with commercially available antibodies. Immunostaining of intact islets showed an islet-wide network involving α- and δ-cells. Furthermore, we used immunostaining to compare the islet architecture as pertaining to δ-cell number, and morphology between islets from healthy human donors and type 2 diabetic donors and found that the number of δ-cells in type 2 diabetic islets is reduced. In paper III we expressed ChR2 in α- and δ-cells in two novel mouse models. We showed that photoactivation of α-cells depolarized the α-cells and evoked action potential firing, effects that were associated with stimulation of glucagon secretion regardless of the glucose concentration. In islets exposed to 1 mM glucose, photoactivation of δ-cells transiently hyperpolarized α-cells, produced a long-lasting inhibition of glucagon exocytosis and inhibited glucagon secretion at 1 mM glucose but had no additional inhibitory effect at 6 or 20 mM glucose. The effect of somatostatin was so strong that it was possible to suppress glucagon secretion by photoactivation of δ-cells even when measurements were performed using the perfused mouse pancreas.","abstract_has_math":false,"creators":["Miranda, Caroline"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-06-12","date_published":"2020-06-12","updated_at":"2026-08-21T22:21:56Z","subjects":["Type 2 Diabetes","Glucagon","α-Cell","Optogenetics"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2077/64544","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"source_record":{"url":"https://gupea.ub.gu.se/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Agupea.ub.gu.se%3A2077%2F64544","prefix":"dim"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Miranda, Caroline"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2020-06-12T13:50:29Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2020-06-12T13:50:29Z"]},{"key":"dc:date.issued","label":"Date","values":["2020-06-12"]},{"key":"dc:type","label":"Dc Type","values":["text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Type 2 Diabetes","Glucagon","α-Cell","Optogenetics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2077/64544"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["ABSTRACT The mechanisms controlling glucagon secretion by α-cells in islets of Langerhans were studied. We generated mice with the light-activated ion channel ChR2 specifically expressed in β-, α-, and δ-cells, and explored the spatio-temporal relationship between cell activation and glucagon release. In paper I, ChR2 was expressed in β-cells and photoactivation of these cells rapidly depolarized neighbouring δ-cell but produced a more delayed effect on α-cells. We showed that these effects were mediated via electrical signalling from the β- to δ-cells via gapjunction. Once activated, the δ-cells released somatostatin which repolarized the αcells following its intercellular diffusion from the δ- to the α-cells. In paper II we used a novel antibody for detection of somatostatin, which showed great efficiency compared with commercially available antibodies. Immunostaining of intact islets showed an islet-wide network involving α- and δ-cells. Furthermore, we used immunostaining to compare the islet architecture as pertaining to δ-cell number, and morphology between islets from healthy human donors and type 2 diabetic donors and found that the number of δ-cells in type 2 diabetic islets is reduced. In paper III we expressed ChR2 in α- and δ-cells in two novel mouse models. We showed that photoactivation of α-cells depolarized the α-cells and evoked action potential firing, effects that were associated with stimulation of glucagon secretion regardless of the glucose concentration. In islets exposed to 1 mM glucose, photoactivation of δ-cells transiently hyperpolarized α-cells, produced a long-lasting inhibition of glucagon exocytosis and inhibited glucagon secretion at 1 mM glucose but had no additional inhibitory effect at 6 or 20 mM glucose. The effect of somatostatin was so strong that it was possible to suppress glucagon secretion by photoactivation of δ-cells even when measurements were performed using the perfused mouse pancreas."]},{"key":"dc:title","label":"Title","values":["Paracrine control of glucagon secretion in the pancreatic α-cell: Studies involving optogenetic cell activation"]}]}],"canonical_facts":{"dc:creator":["Miranda, Caroline"],"dc:date.accessioned":["2020-06-12T13:50:29Z"],"dc:date.available":["2020-06-12T13:50:29Z"],"dc:date.issued":["2020-06-12"],"dc:description.abstract":["ABSTRACT The mechanisms controlling glucagon secretion by α-cells in islets of Langerhans were studied. We generated mice with the light-activated ion channel ChR2 specifically expressed in β-, α-, and δ-cells, and explored the spatio-temporal relationship between cell activation and glucagon release. In paper I, ChR2 was expressed in β-cells and photoactivation of these cells rapidly depolarized neighbouring δ-cell but produced a more delayed effect on α-cells. We showed that these effects were mediated via electrical signalling from the β- to δ-cells via gapjunction. Once activated, the δ-cells released somatostatin which repolarized the αcells following its intercellular diffusion from the δ- to the α-cells. In paper II we used a novel antibody for detection of somatostatin, which showed great efficiency compared with commercially available antibodies. Immunostaining of intact islets showed an islet-wide network involving α- and δ-cells. Furthermore, we used immunostaining to compare the islet architecture as pertaining to δ-cell number, and morphology between islets from healthy human donors and type 2 diabetic donors and found that the number of δ-cells in type 2 diabetic islets is reduced. In paper III we expressed ChR2 in α- and δ-cells in two novel mouse models. We showed that photoactivation of α-cells depolarized the α-cells and evoked action potential firing, effects that were associated with stimulation of glucagon secretion regardless of the glucose concentration. In islets exposed to 1 mM glucose, photoactivation of δ-cells transiently hyperpolarized α-cells, produced a long-lasting inhibition of glucagon exocytosis and inhibited glucagon secretion at 1 mM glucose but had no additional inhibitory effect at 6 or 20 mM glucose. The effect of somatostatin was so strong that it was possible to suppress glucagon secretion by photoactivation of δ-cells even when measurements were performed using the perfused mouse pancreas."],"dc:identifier.uri":["http://hdl.handle.net/2077/64544"],"dc:language.iso":["eng"],"dc:subject":["Type 2 Diabetes","Glucagon","α-Cell","Optogenetics"],"dc:title":["Paracrine control of glucagon secretion in the pancreatic α-cell: Studies involving optogenetic cell activation"],"dc:type":["text"]},"updated_at":"2026-08-21T22:21:56Z"}