Academic Journal
4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
| العنوان: | 4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity |
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| المؤلفون: | de Pablo, Sara, Rodríguez-Comas, Júlia, Díaz-Catalán, Daniela, Alcarraz-Vizán, Gema, Castaño, Carlos, Moreno-Vedia, Juan, Montane, Joel, Parrizas, Marcelina, Servitja, Joan-Marc, Novials, Anna |
| المساهمون: | Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas |
| المصدر: | Scientific Reports ; volume 11, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2021 |
| الوصف: | Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). 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 vy ) mice that overexpress hIAPP in β cells (A vy hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when A vy hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese A vy 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 vy 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-021-91311-2 |
| الاتاحة: | http://dx.doi.org/10.1038/s41598-021-91311-2 https://www.nature.com/articles/s41598-021-91311-2.pdf https://www.nature.com/articles/s41598-021-91311-2 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.267170A4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-021-91311-2 |
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