Expansion Of Islet-Resident Macrophages Leads To Inflammation Affecting Beta Cell Proliferation And Function In Obesity

The nature of obesity-associated islet inflammation and its impact on beta cell abnormalities remains poorly defined. Here, we explore immune cell components of islet inflammation and define their roles in regulating beta cell function and proliferation. Islet inflammation in obese mice is dominated by macrophages. We identify two islet-resident macrophage populations, characterized by their anatomical distributions, distinct phenotypes, and functional properties. Obesity induces the local expansion of resident intraislet macrophages, independent of recruitment from circulating monocytes. Functionally, intra-islet macrophages impair beta cell function in a cell-cell contact-dependent manner. Increased engulfment of beta cell insulin secretory granules by intra-islet macrophages in obese mice may contribute to restricting insulin secretion. In contrast, both intra- and peri-islet macrophage populations from obese mice promote beta cell proliferation in a PDGFR signaling-dependent manner. Together, these data define distinct roles and mechanisms for islet macrophages in the regulation of islet beta