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Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Methylglyoxal was found to induce the formation of insulin native-like aggregates and reduce protein fibrillation by blocking the formation of the seeding<jats:italic>nuclei<\/jats:italic>. Equilibrium-unfolding experiments using chaotropic agents showed that glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration (smaller m-value). Our observations suggest that methylglyoxal modification of insulin leads to a less compact and less stable structure that may be associated to an increased protein dynamics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We propose that higher dynamics in glycated insulin could prevent the formation of the rigid cross-\u03b2 core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2091-12-41","type":"journal-article","created":{"date-parts":[[2011,8,5]],"date-time":"2011-08-05T18:23:05Z","timestamp":1312568585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation"],"prefix":"10.1186","volume":"12","author":[{"given":"Luis MA","family":"Oliveira","sequence":"first","affiliation":[]},{"given":"Ana","family":"Lages","sequence":"additional","affiliation":[]},{"given":"Ricardo A","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Henrique","family":"Neves","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Fam\u00edlia","sequence":"additional","affiliation":[]},{"given":"Ana V","family":"Coelho","sequence":"additional","affiliation":[]},{"given":"Alexandre","family":"Quintas","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2011,8,5]]},"reference":[{"issue":"4","key":"352_CR1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1056\/NEJM199907223410406","volume":"341","author":"PR Shepherd","year":"1999","unstructured":"Shepherd PR, Kahn BB: Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus. 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