Inflammatory Cytokines Rewire the Proinsulin Interaction Network in Human Islets.

ABSTRACT:

Context

Aberrant biosynthesis and secretion of the insulin precursor proinsulin occurs in both type I and type II diabetes. Inflammatory cytokines are implicated in pancreatic islet stress and dysfunction in both forms of diabetes, but the mechanisms remain unclear.

Objective

We sought to determine the effect of the diabetes-associated cytokines on proinsulin folding, trafficking, secretion, and β-cell function.

Methods

Human islets were treated with interleukin-1β and interferon-γ for 48 hours, followed by analysis of interleukin-6, nitrite, proinsulin and insulin release, RNA sequencing, and unbiased profiling of the proinsulin interactome by affinity purification-mass spectrometry.

Results

Cytokine treatment induced secretion of interleukin-6, nitrites, and

SUBMITTER: Tran DT 

PROVIDER: S-EPMC10233482 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature