Amyloid formation disrupts the balance between interleukin-1β and interleukin-1 receptor antagonist in human islets.

ABSTRACT:

Objectives

β-cell dysfunction and apoptosis associated with islet inflammation play a key role in the pathogenesis of type 2 diabetes (T2D). Growing evidence suggests that islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and β-cell death in T2D. We recently showed the role of interleukin-1β (IL-1β)/Fas/caspase-8 apoptotic pathway in amyloid-induced β-cell death. In this study, we used human islets in culture as an ex vivo model of amyloid formation to: (1) investigate the effects of amyloid on islet levels of the natural IL-1 receptor antagonist (IL-1Ra); (2) examine if modulating the IL-1β/IL-1Ra balance can prevent amyloid-induced β-cell Fas upregulation and apoptosis.

Methods

Isolated human islets (n

SUBMITTER: Hui Q 

PROVIDER: S-EPMC5518725 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature