Macrophage-associated pro-inflammatory state in human islets from obese individuals.
Wei HeTing YuanKathrin MaedlerPublished in: Nutrition & diabetes (2019)
Obesity is associated with inflammatory macrophages in insulin responsive tissues and the resulting inflammatory response is a major contributor to insulin resistance. In insulin-producing pancreatic islets, the intra-islet accumulation of macrophages is observed in patients of type 2 diabetes (T2D), but such has not been investigated in obese individuals. Here, we show that pro-inflammatory cytokines (IL-1β, IL-6, and TNF), anti-inflammatory cytokines (IL-10 and TGF-β) and macrophage polarization markers (CD11c, CD163, and NOS2) were expressed in isolated human islets from non-diabetic donors. Clodronate-mediated depletion of resident macrophages revealed expression of IL1B and IL10 mostly from macrophages, while IL6, TNF, and TGFB1 came largely from a non-macrophage origin in human islets. NOS2 expression came exclusively from non-macrophage cells in non-obese individuals, while it originated also from macrophages in obese donors. Macrophage marker expression of CD68, CD163, and ITGAX was unchanged in islets of non-obese control and obese cohorts. In contrast, IL1B and NOS2 were significantly increased in islets from obese, compared to non-obese individuals, implying a more inflammatory macrophage phenotype in islets in obesity. Our study shows elevated macrophage-associated inflammation in human islets in obesity, which could be an initiating factor to the pro-inflammatory intra-islet milieu and contribute to the higher susceptibility to T2D in obese individuals.
Keyphrases
- adipose tissue
- weight loss
- type diabetes
- metabolic syndrome
- insulin resistance
- endothelial cells
- bariatric surgery
- obese patients
- poor prognosis
- inflammatory response
- oxidative stress
- glycemic control
- induced pluripotent stem cells
- gene expression
- physical activity
- magnetic resonance
- nitric oxide synthase
- induced apoptosis
- magnetic resonance imaging
- pluripotent stem cells
- transforming growth factor
- body mass index
- patient safety
- long non coding rna
- single cell
- newly diagnosed
- toll like receptor
- skeletal muscle
- signaling pathway
- endoplasmic reticulum stress
- nitric oxide
- nk cells
- cancer therapy
- patient reported outcomes
- cell proliferation
- quality improvement