Amyloid formation reduces protein kinase B phosphorylation in primary islet β-cells which is improved by blocking IL-1β signaling

PloS One
Yun ZhangLucy Marzban

Abstract

Amyloid formation in the pancreatic islets due to aggregation of human islet amyloid polypeptide (hIAPP) contributes to reduced β-cell mass and function in type 2 diabetes (T2D) and islet transplantation. Protein kinase B (PKB) signaling plays a key role in the regulation of β-cell survival, function and proliferation. In this study, we used human and hIAPP-expressing transgenic mouse islets in culture as two ex vivo models of human islet amyloid formation to: 1. Investigate the effects of amyloid formation on PKB phosphorylation in primary islet β-cells; 2. Test if inhibition of amyloid formation and/or interleukin-1β (IL-1β) signaling in islets can restore the changes in β-cell phospho-PKB levels mediated by amyloid formation. Human and hIAPP-expressing mouse islets were cultured in elevated glucose with an amyloid inhibitor (Congo red) or embedded within collagen matrix to prevent amyloid formation. To block the IL-1β signaling, human islets were treated with an IL-1 receptor antagonist (anakinra) or a glucagon-like peptide-1 agonist (exenatide). β-cell phospho-PKB levels, proliferation, apoptosis, islet IL-1β levels and amyloid formation were assessed. Amyloid formation in both cultured human and hIAPP-expressing mouse isle...Continue Reading

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Citations

Nov 20, 2018·Antioxidants & Redox Signaling·Petr JežekLydie Plecitá-Hlavatá
Dec 12, 2019·Frontiers in Neuroscience·Liam GraciaUmesh K Jinwal
Jun 3, 2021·International Journal of Molecular Sciences·Safia CostesMagalie A Ravier
Oct 13, 2021·Journal of Cellular Physiology·Carine MarmentiniMirian A Kurauti

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Methods Mentioned

BETA
transgenic
ELISA

Software Mentioned

Pro analyzer
Image
Image Lab

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