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Treatment with chaperones has been associated with a decrease in endoplasmic reticulum stress leading to improved glucose metabolism. The aim of this work was to investigate whether the chemical chaperone 4-phenylbutyrate (PBA) prevents glucose metabolism abnormalities and amyloid deposition in obese agouti viable yellow (A\n                    <jats:sup>vy<\/jats:sup>\n                    ) mice that overexpress hIAPP in \u03b2 cells (A\n                    <jats:sup>vy<\/jats:sup>\n                    hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8\u00a0weeks of age, when A\n                    <jats:sup>vy<\/jats:sup>\n                    hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese A\n                    <jats:sup>vy<\/jats:sup>\n                    hIAPP mice in fasting and fed conditions throughout the study. This effect was paralleled by a decrease in hyperinsulinemia. Importantly, PBA treatment reduced the prevalence and the severity of islet amyloid deposition in A\n                    <jats:sup>vy<\/jats:sup>\n                    hIAPP mice. Collectively, these results show that PBA treatment elicits a marked reduction of hyperglycemia and reduces amyloid deposits in obese and diabetic mice, highlighting the potential of chaperones for T2D treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-91311-2","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T06:04:47Z","timestamp":1622786687000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity"],"prefix":"10.1038","volume":"11","author":[{"given":"Sara","family":"de Pablo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Rodr\u00edguez-Comas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"D\u00edaz-Catal\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Alcarraz-Viz\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Moreno-Vedia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Montane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelina","family":"Parrizas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan-Marc","family":"Servitja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Novials","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"issue":"8","key":"91311_CR1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/S1471-4914(02)02377-8","volume":"8","author":"MK Lingohr","year":"2002","unstructured":"Lingohr, M. 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