Abstract:

Objective: To explore the effects of α-lipoic acid (LA) and acetyl-L-carnitine (ALC) on islet cell dysfunction.
Methods: LA and ALC were co-incubated with a combination of three cytokines, i.e. tumor necrosis factor-α (TNF-α),
interleukin-1β (IL-1β) and interferon-γ (IFN-γ) for 48 h, to establish TII-treated rat insulinoma cell lines (Rin-m5F cells).
Cell viability was detected with MTT assay and cell morphology was examined with the imunofluorescence technique.
Reactive oxygen species (ROS) were measured with flow cytometry. The expression levels of apoptotic-related proteins
including Bax, Caspase-3, NF-κB and Bcl-2 were examined via Western blotting analysis. Insulin level was measured
through radioimmunoassay (RIA). Results: Treatment of rats with TII for 48 h significantly decreased RIN-m5f cells
viability, and basal and glucose-stimulated insulin secretion. TII significantly increased ROS and nitrite oxide (NO) levels,
promoted NF-κB translocation into nucleus. TII increased NF-κB, Bax and Caspase-3 expression, inhibited I-κB and
Bcl-2 expression. In addition, TII increased cytochrome c release from mitochondira. A combination of LA and ALC
was seen to facilitate improvement of TII-induced islet cell dysfunction, increase RIN-m5f cells viability and basal and
glucose-stimulated insulin secretion, decrease ROS and NO levels, inhibit NF-κB translocation into nucleus, decrease
NF-κB, Bax and Caspase-3 expression and increase I-κB and Bcl-2 expression. LA＋ALC decreased cytochrome c
release from mitochondria. Conclusions: TII can induce RIN-m5f cells dysfunction and inhibit insulin secretion via
ROS-mitochondria- apoptosis-NF-κB-NOS-NO pathway. LA＋ALC can facilitate RIN-m5f cells function via ROSmitochondria
apoptosis-NF-κB-NOS-NO pathway.

Key words: cytokine, islet cell dysfunction, α-lipoic acid, acetyl-L-carnitine