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Amylin: difference between revisions

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CuriousCallum (talk)
expand §Amyloid formation
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Revision 25 — 16:05, 17 Sep 2025
TirzTaxonomist (talk)
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44Islet amyloid is present in the majority of pancreases examined post mortem from people with long-standing type 2 diabetes. Whether it is a cause of beta-cell loss or a consequence of prolonged secretory stress remains debated; oligomeric intermediates rather than mature fibrils are the species most often proposed as cytotoxic.44Islet amyloid is present in the majority of pancreases examined post mortem from people with long-standing type 2 diabetes. Whether it is a cause of beta-cell loss or a consequence of prolonged secretory stress remains debated; oligomeric intermediates rather than mature fibrils are the species most often proposed as cytotoxic.
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+46The practical consequence for peptide chemistry is that human amylin is a difficult peptide to handle: it aggregates in solution at ordinary concentrations, and any preparation of it requires attention to solvent, concentration and time. The engineered analogue pramlintide replaces three residues with prolines, which disrupts β-sheet formation and makes a stable formulation possible. Aggregation is accordingly a specification attribute for this chemistry rather than an incidental observation. See [[Peptide aggregation]].{{r|westermark2011,usp1503}}
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46== References ==48== References ==
47{{reflist}}49{{reflist}}
48<ref name="hay2015">Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. "Amylin: pharmacology, physiology, and clinical potential." ''Pharmacological Reviews'' 67(3):564–600 (2015). DOI:10.1124/pr.115.010629. PMID 26071095.</ref>50<ref name="hay2015">Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. "Amylin: pharmacology, physiology, and clinical potential." ''Pharmacological Reviews'' 67(3):564–600 (2015). DOI:10.1124/pr.115.010629. PMID 26071095.</ref>
49<ref name="westermark2011">Westermark P, Andersson A, Westermark GT. "Islet amyloid polypeptide, islet amyloid, and diabetes mellitus." ''Physiological Reviews'' 91(3):795–826 (2011). DOI:10.1152/physrev.00042.2009. PMID 21742788.</ref>51<ref name="westermark2011">Westermark P, Andersson A, Westermark GT. "Islet amyloid polypeptide, islet amyloid, and diabetes mellitus." ''Physiological Reviews'' 91(3):795–826 (2011). DOI:10.1152/physrev.00042.2009. PMID 21742788.</ref>
+52<ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref>
50<ref name="campbell2013">Campbell JE, Drucker DJ. "Pharmacology, physiology, and mechanisms of incretin hormone action." ''Cell Metabolism'' 17(6):819–837 (2013). PMID 23684623.</ref>53<ref name="campbell2013">Campbell JE, Drucker DJ. "Pharmacology, physiology, and mechanisms of incretin hormone action." ''Cell Metabolism'' 17(6):819–837 (2013). PMID 23684623.</ref>
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