Islet amylin polypeptide (IAPP) is co-secreted along with insulin in the pancreatic islets of Langerhans. During type 2 diabetes mellitus, human IAPP (hIAPP) fibrilizes to form amyloid deposits that are found post-mortem in more than 95% of people with the disease. Rodents do not suffer from type 2 diabetes mellitus as their IAPP (rIAPP) does not undergo self-aggregation. Although the amyloid deposit is found in those with the disease, the actual cause of the disease is the cytotoxicity of the mechanism that forms those amyloid deposits. The self-aggregation of IAPP to form amyloid deposits is inhibited by insulin due to the aromatic π-stacking at the site where IAPP fibrilizes with itself and binds with insulin. Knowing this, the binding site of both rIAPP and hIAPP (10-19) was synthesized, as was the binding site of insulin (14-18). The tyrosine in the active site of insulin was replaced with an unnatural amino acid (n-methyl tyrosine) but synthesis failed repeatedly. The ability of hIAPP 10-19 to disrupt membranes was tested using a dye leakage assay. The fluorescence of the peptide was measured in increasing concentrations to determine whether their ability to cause cell death is concentration dependent or not. While the rate of membrane disruption stayed constant, it was determined that overall permeability increased with concentration of hIAPP 10-19.
","abstract_html":"<p>Islet amylin polypeptide (IAPP) is co-secreted along with insulin in the pancreatic islets of Langerhans. During type 2 diabetes mellitus, human IAPP (hIAPP) fibrilizes to form amyloid deposits that are found post-mortem in more than 95% of people with the disease. Rodents do not suffer from type 2 diabetes mellitus as their IAPP (rIAPP) does not undergo self-aggregation. Although the amyloid deposit is found in those with the disease, the actual cause of the disease is the cytotoxicity of the mechanism that forms those amyloid deposits. The self-aggregation of IAPP to form amyloid deposits is inhibited by insulin due to the aromatic π-stacking at the site where IAPP fibrilizes with itself and binds with insulin. Knowing this, the binding site of both rIAPP and hIAPP (10-19) was synthesized, as was the binding site of insulin (14-18). The tyrosine in the active site of insulin was replaced with an unnatural amino acid (n-methyl tyrosine) but synthesis failed repeatedly. The ability of hIAPP 10-19 to disrupt membranes was tested using a dye leakage assay. The fluorescence of the peptide was measured in increasing concentrations to determine whether their ability to cause cell death is concentration dependent or not. While the rate of membrane disruption stayed constant, it was determined that overall permeability increased with concentration of hIAPP 10-19.</p>","abstract_has_math":false,"creators":["Gray, Andrew William"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Open Access Thesis","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Deborah Heyl-Clegg, PhD, Chair","Dr. Steven Pernecky, PhD","Dr. Ruth Ann Armitage, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-01-01T08:00:00Z","date_published":"2008-01-01T08:00:00Z","updated_at":"2026-07-24T02:16:36Z","subjects":["Amyloid Research","Polypeptides Research","Diabetes Research","Chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.emich.edu/theses/203","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Deborah Heyl-Clegg, PhD, Chair","Dr. Steven Pernecky, PhD","Dr. Ruth Ann Armitage, PhD"]},{"key":"dc:creator","label":"Author","values":["Gray, Andrew William"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Amyloid Research","Polypeptides Research","Diabetes Research","Chemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.emich.edu/theses/203"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Islet amylin polypeptide (IAPP) is co-secreted along with insulin in the pancreatic islets of Langerhans. During type 2 diabetes mellitus, human IAPP (hIAPP) fibrilizes to form amyloid deposits that are found post-mortem in more than 95% of people with the disease. Rodents do not suffer from type 2 diabetes mellitus as their IAPP (rIAPP) does not undergo self-aggregation. Although the amyloid deposit is found in those with the disease, the actual cause of the disease is the cytotoxicity of the mechanism that forms those amyloid deposits. The self-aggregation of IAPP to form amyloid deposits is inhibited by insulin due to the aromatic π-stacking at the site where IAPP fibrilizes with itself and binds with insulin. Knowing this, the binding site of both rIAPP and hIAPP (10-19) was synthesized, as was the binding site of insulin (14-18). The tyrosine in the active site of insulin was replaced with an unnatural amino acid (n-methyl tyrosine) but synthesis failed repeatedly. The ability of hIAPP 10-19 to disrupt membranes was tested using a dye leakage assay. The fluorescence of the peptide was measured in increasing concentrations to determine whether their ability to cause cell death is concentration dependent or not. While the rate of membrane disruption stayed constant, it was determined that overall permeability increased with concentration of hIAPP 10-19.
"]},{"key":"dc:title","label":"Title","values":["Synthesis and dye leakage assay of human and rat islet amyloid polypeptide 10-19 and insulin 14-18"]}]}],"canonical_facts":{"dc:contributor":["Deborah Heyl-Clegg, PhD, Chair","Dr. Steven Pernecky, PhD","Dr. Ruth Ann Armitage, PhD"],"dc:creator":["Gray, Andrew William"],"dc:description.abstract":["Islet amylin polypeptide (IAPP) is co-secreted along with insulin in the pancreatic islets of Langerhans. During type 2 diabetes mellitus, human IAPP (hIAPP) fibrilizes to form amyloid deposits that are found post-mortem in more than 95% of people with the disease. Rodents do not suffer from type 2 diabetes mellitus as their IAPP (rIAPP) does not undergo self-aggregation. Although the amyloid deposit is found in those with the disease, the actual cause of the disease is the cytotoxicity of the mechanism that forms those amyloid deposits. The self-aggregation of IAPP to form amyloid deposits is inhibited by insulin due to the aromatic π-stacking at the site where IAPP fibrilizes with itself and binds with insulin. Knowing this, the binding site of both rIAPP and hIAPP (10-19) was synthesized, as was the binding site of insulin (14-18). The tyrosine in the active site of insulin was replaced with an unnatural amino acid (n-methyl tyrosine) but synthesis failed repeatedly. The ability of hIAPP 10-19 to disrupt membranes was tested using a dye leakage assay. The fluorescence of the peptide was measured in increasing concentrations to determine whether their ability to cause cell death is concentration dependent or not. While the rate of membrane disruption stayed constant, it was determined that overall permeability increased with concentration of hIAPP 10-19.
"],"dc:identifier":["https://commons.emich.edu/theses/203"],"dc:subject":["Amyloid Research","Polypeptides Research","Diabetes Research","Chemistry"],"dc:title":["Synthesis and dye leakage assay of human and rat islet amyloid polypeptide 10-19 and insulin 14-18"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Open Access Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T02:16:36Z"}