Macrophage-associated pro-inflammatory state in human islets from obese individuals

Area of Science:

• Endocrinology
• Immunology
• Metabolic Diseases

Background:

• Obesity is linked to inflammation and insulin resistance in insulin-sensitive tissues.
• Macrophages accumulate in pancreatic islets of type 2 diabetes (T2D) patients, but their role in obesity-associated islet inflammation is unclear.

Purpose of the Study:

• To investigate macrophage presence and inflammatory status within human islets from obese and non-obese donors.
• To determine the origin of cytokine and macrophage marker expression in human islets.

Main Methods:

• Isolated human islets from non-diabetic donors were analyzed for cytokine and macrophage marker expression.
• Clodronate-mediated depletion was used to identify macrophage-derived gene expression.
• Islets from obese and non-obese individuals were compared for inflammatory markers.

Main Results:

• Pro-inflammatory (IL-1β, IL-6, TNF) and anti-inflammatory (IL-10, TGF-β) cytokines and macrophage markers were detected in human islets.
• Macrophages were a primary source of IL-1β and IL-10, while other cytokines originated from non-macrophage cells.
• Obese individuals showed increased IL-1β and NOS2 expression in islets, with NOS2 originating from macrophages, unlike in non-obese individuals.

Conclusions:

• Obesity is associated with elevated macrophage-derived inflammation within human pancreatic islets.
• This intra-islet inflammation may contribute to the pro-inflammatory environment and increased T2D susceptibility in obesity.