{"id":{"repo_id":"nott-trent","oai_identifier":"oai:irep.ntu.ac.uk:323"},"canonical_url":"https://search.dev.ndltd.org/etd/nott-trent/oai:irep.ntu.ac.uk:323","repository":{"repo_id":"nott-trent","name":"Nottingham Trent University","base_url":"https://irep.ntu.ac.uk/cgi/oai2"},"display":{"title":"Transglutaminase in the life and death of the pancreatic β-cell","abstract":"Tissue transglutaminase (TG2) is a ubiquitous enzyme that catalyses both the Ca2+-dependent formation of protein cross-links via intermolecular isopeptide bonds, and the Ca2+-independent hydrolysis of GTP. The multifunctional nature of the TG2 protein has been reported in numerous intracellular mechanisms, cell-surface associations, and extracellular matrix (ECM) interactions. In the pancreas, the expression of TG may be fundamental to the insulin-secretion function of β-cells, and associated diabetic disorders. The functional roles of TG2 in the pancreas were investigated in the present study using in vitro models of rat pancreatic insulinoma β-cells (BRIN-BD11), and ex vivo islet of Langerhans models from human, rat, TG2(-/-) knockout mice and their wild-type counterparts. The importance of ECM-associated TG2 in the maintenance of β-cell survival and function was also investigated using an in vitro human urinary bladder carcinoma support matrix (5637 cells). Biochemical analysis of both clonal BRIN-BD11 and islet β-cells showed a thiol-dependent TG2 activity mechanism that was reciprocally regulated by Ca2+ and GTP.","abstract_html":"Tissue transglutaminase (TG2) is a ubiquitous enzyme that catalyses both the Ca2+-dependent formation of protein cross-links via intermolecular isopeptide bonds, and the Ca2+-independent hydrolysis of GTP. The multifunctional nature of the TG2 protein has been reported in numerous intracellular mechanisms, cell-surface associations, and extracellular matrix (ECM) interactions. In the pancreas, the expression of TG may be fundamental to the insulin-secretion function of β-cells, and associated diabetic disorders. The functional roles of TG2 in the pancreas were investigated in the present study using in vitro models of rat pancreatic insulinoma β-cells (BRIN-BD11), and ex vivo islet of Langerhans models from human, rat, TG2(-/-) knockout mice and their wild-type counterparts. The importance of ECM-associated TG2 in the maintenance of β-cell survival and function was also investigated using an in vitro human urinary bladder carcinoma support matrix (5637 cells). Biochemical analysis of both clonal BRIN-BD11 and islet β-cells showed a thiol-dependent TG2 activity mechanism that was reciprocally regulated by Ca2+ and GTP.","abstract_has_math":false,"creators":["Dookie, S"],"institution":"Nottingham Trent University","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010","date_published":"2010","updated_at":"2026-07-24T06:30:49Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Dookie, S"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010"]},{"key":"dc:date.issued","label":"Date","values":["2010"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["Nottingham Trent University"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://irep.ntu.ac.uk/id/eprint/323/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://irep.ntu.ac.uk/id/eprint/323/1/216250_2011_PhD_Dookie_Shakthi%20complete.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Tissue transglutaminase (TG2) is a ubiquitous enzyme that catalyses both the Ca2+-dependent formation of protein cross-links via intermolecular isopeptide bonds, and the Ca2+-independent hydrolysis of GTP. The multifunctional nature of the TG2 protein has been reported in numerous intracellular mechanisms, cell-surface associations, and extracellular matrix (ECM) interactions. In the pancreas, the expression of TG may be fundamental to the insulin-secretion function of β-cells, and associated diabetic disorders. The functional roles of TG2 in the pancreas were investigated in the present study using in vitro models of rat pancreatic insulinoma β-cells (BRIN-BD11), and ex vivo islet of Langerhans models from human, rat, TG2(-/-) knockout mice and their wild-type counterparts. The importance of ECM-associated TG2 in the maintenance of β-cell survival and function was also investigated using an in vitro human urinary bladder carcinoma support matrix (5637 cells). Biochemical analysis of both clonal BRIN-BD11 and islet β-cells showed a thiol-dependent TG2 activity mechanism that was reciprocally regulated by Ca2+ and GTP."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Transglutaminase in the life and death of the pancreatic β-cell"]}]}],"canonical_facts":{"dc:creator":["Dookie, S"],"dc:date":["2010"],"dc:date.issued":["2010"],"dc:description.abstract":["Tissue transglutaminase (TG2) is a ubiquitous enzyme that catalyses both the Ca2+-dependent formation of protein cross-links via intermolecular isopeptide bonds, and the Ca2+-independent hydrolysis of GTP. The multifunctional nature of the TG2 protein has been reported in numerous intracellular mechanisms, cell-surface associations, and extracellular matrix (ECM) interactions. In the pancreas, the expression of TG may be fundamental to the insulin-secretion function of β-cells, and associated diabetic disorders. The functional roles of TG2 in the pancreas were investigated in the present study using in vitro models of rat pancreatic insulinoma β-cells (BRIN-BD11), and ex vivo islet of Langerhans models from human, rat, TG2(-/-) knockout mice and their wild-type counterparts. The importance of ECM-associated TG2 in the maintenance of β-cell survival and function was also investigated using an in vitro human urinary bladder carcinoma support matrix (5637 cells). Biochemical analysis of both clonal BRIN-BD11 and islet β-cells showed a thiol-dependent TG2 activity mechanism that was reciprocally regulated by Ca2+ and GTP."],"dc:format":["text"],"dc:identifier.uri":["https://irep.ntu.ac.uk/id/eprint/323/1/216250_2011_PhD_Dookie_Shakthi%20complete.pdf"],"dc:language":["en"],"dc:publisher.institution":["Nottingham Trent University"],"dc:relation.isreferencedby":["https://irep.ntu.ac.uk/id/eprint/323/"],"dc:title":["Transglutaminase in the life and death of the pancreatic β-cell"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T06:30:49Z"}