The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival
المؤلفون المشاركون
Greco, Annalisa
Mancuso, Elettra
Arcidiacono, Gaetano Paride
Musca, Donatella
Procopio, Teresa
Ruffo, Mariafrancesca
Sesti, Giorgio
Hribal, Marta Letizia
المصدر
International Journal of Endocrinology
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-10، 10ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-01-03
دولة النشر
مصر
عدد الصفحات
10
التخصصات الرئيسية
الملخص EN
Currently available antidiabetic treatments fail to halt, and may even exacerbate, pancreatic β-cell exhaustion, a key feature of type 2 diabetes pathogenesis; thus, strategies to prevent, or reverse, β-cell failure should be actively sought.
The serine threonine kinase Akt has a key role in the regulation of β-cell homeostasis; among Akt modulators, a central role is played by pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) family.
Here, taking advantage of an in vitro model of chronic exposure to high glucose, we demonstrated that PHLPPs, particularly the second family member called PHLPP2, are implicated in the ability of pancreatic β cells to deal with glucose toxicity.
We observed that INS-1 rat pancreatic β cell line maintained for 12–15 passages at high (30 mM) glucose concentrations (INS-1 HG) showed increased expression of PHLPP2 and PHLPP1 both at mRNA and protein level as compared to INS-1 maintained for the same number of passages in the presence of normal glucose levels (INS-1 NG).
These changes were paralleled by decreased phosphorylation of Akt and by increased expression of apoptotic and autophagic markers.
To investigate if PHLPPs had a casual role in the alteration of INS-1 homeostasis observed upon chronic exposure to high glucose concentrations, we took advantage of shRNA technology to specifically knock-down PHLPPs.
We obtained proof-of-concept evidence that modulating PHLPPs expression may help to restore a healthy β cell mass, as the reduced expression of PHLPP2/1 was accompanied by a recovered balance between pro- and antiapoptotic factor levels.
In conclusion, our data provide initial support for future studies aimed to identify pharmacological PHLPPs modulator to treat beta-cell survival impairment.
They also contribute to shed some light on β-cell dysfunction, a complex and unsatisfactorily characterized phenomenon that has a central causative role in the pathogenesis of type 2 diabetes.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Hribal, Marta Letizia& Mancuso, Elettra& Arcidiacono, Gaetano Paride& Greco, Annalisa& Musca, Donatella& Procopio, Teresa…[et al.]. 2020. The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival. International Journal of Endocrinology،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1170058
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Hribal, Marta Letizia…[et al.]. The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival. International Journal of Endocrinology No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1170058
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Hribal, Marta Letizia& Mancuso, Elettra& Arcidiacono, Gaetano Paride& Greco, Annalisa& Musca, Donatella& Procopio, Teresa…[et al.]. The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival. International Journal of Endocrinology. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1170058
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1170058
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر