Role of interleukin-1 in mediating the toxic effect of human islet amyloid polypeptide on pancreatic islet cells

Objective To explore the role of interleukin-1 (IL-1) in human islet amyloid polypeptide (iAPP) related pancreatic islet cell toxicity. Methods Pancreatic islets were isolated from adult Wistar rats and the cell vitality was identified. The islets were divided into control islets (group A), 10 μmol/L iAPP incubated islets (group B), 10 μmol/L iAPP plus 10 mg/L IL-1 receptor blocker (IL-1Ra) co-incubated islets (group C) and incubated for 24 h. Annexin-V/propidium iodide (PI) double-staining was used to detect islet cell apoptosis. The expressions of inflammation-related and apoptosis-related genes Bax Bcl-2 mRNA were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Independent sample t test was used for comparison between two groups. LSD test was used to compare the differences among three groups. Results (1) The apoptosis ratio and apoptosis-related gene expression: the apoptosis ratio in group B increased significantly than those in group A [(16.8±4.7)% vs (1.2±0.4)%]; while the apoptosis ratio in group C[(4.4±2.1)%] was significantly lower than those in group B (t=5.72, 4.17, respectively, both P<0.05). Consistently, the expression of Bax mRNA increased (2.28±0.46) times and Bcl-2 mRNA decreased (0.42±0.18) times in group B than those in group A (t=4.27, 3.10, respectively, both P<0.05). The expression of Bax mRNA decreased (0.48±0.17) times and the expression of Bcl-2 mRNA increased (1.93±0.25) times in group C than those in group B, respectively (t=3.41, 3.23, respectively, bothP<0.05). (2) The expressions of the inflammatory factors: the expressions of IL-1β and tumor necrosis factor increased by (4.25±1.64) times and (3.19±1.04) times in group B than those in group A, respectively (t=3.39, 3.49, respectively, both P<0.05); While they decreased by (0.32±0.11) times and (0.28±0.11) times in group C than those in group B, respectively (t=2.94, 3.65, respectively, both P<0.05). Conclusions The apoptosis of iAPP is associated with inflammation and IL-1 may play an important role in the pathogenesis of iAPP related pancreatic islet cell toxicity. Key words: Islet amyloid polypeptide; Inflammation; Interleukins; Apoptosis