Preliminary analysis of immune activation in early onset type 2 diabetes

• Published in: International Journal of Circumpolar Health
• Main Authors: Julia D. Rempel, Juliet Packiasamy, Heather J. Dean, Jonathon McGavock, Alyssa Janke, Mark Collister, Brandy Wicklow, Elizabeth A. C. Sellers
• Format: Article in Journal/Newspaper
• Language: English
• Published: Taylor & Francis Group 2013
• Subjects: early onset type 2 diabetes; TLR4; interleukin 1beta; Arctic medicine. Tropical medicine; RC955-962; Arctic; Circumpolar Health; First Nations; International Journal of Circumpolar Health
• Online Access: https://doi.org/10.3402/ijch.v72i0.21190; https://doaj.org/article/442c846bf5a84829bee2748f890de8ad

Introduction. First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D). In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR) on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population). TLR4 can bind to lipids from bacteria and food sources activating PBMC to produce cytokines tumour necrosis factor (TNF)-α and interleukin (IL)-1β. These cytokines can interfere with insulin signalling. Here, we seek to understand how TLR4 activation may be involved in early onset T2D. We hypothesized that immune cells from youth with T2D (n=8) would be more reactive upon TLR4 stimulation relative to cells from age and body mass index (BMI)-matched controls without T2D (n=8). Methods. Serum samples were assayed for adipokines (adiponectin and leptin), as well as cytokines. Freshly isolated PBMC were examined for immune reactivity upon culture with TLR4 ligands bacterial lipopolysaccharide (LPS, 2 and 0.2 ng/ml) and the fatty acid palmitate (200 µM). Culture supernatants were evaluated for the amount of TNF-α and IL-1β produced by PBMC. Results. Youth with T2D displayed lower median serum adiponectin levels compared to controls (395 vs. 904 ng/ml, p<0.05). PBMC isolated from youth with and without T2D produced similar levels of TNF-α and IL-1β after exposure to the higher LPS concentration. However, at the low LPS dose the T2D cohort exhibited enhanced IL-1β synthesis relative to the control cohort. Additionally, exposure to palmitate resulted in greater IL-1β synthesis in PBMCs isolated from youth with T2D versus controls (p<0.05). These differences in cytokine production corresponded to greater monocyte activation in the T2D cohort. Conclusion. These preliminary results suggest that cellular ...