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Expansion of Islet-Resident Macrophages Leads to Inflammation Affecting β Cell Proliferation and Function in Obesity.

Cell Metab. 2019 Feb 05;29(2):457-474.e5. Epub 2018 Dec 27
Wei Ying 1 , Yun Sok Lee 1 , Yi Dong 2 , Jason S Seidman 3 , Meixiang Yang 4 , Roi Isaac 1 , Jong Bae Seo 1 , Bi-Huei Yang 2 , Joshua Wollam 1 , Matthew Riopel 1 , Joanne McNelis 1 , Christopher K Glass 3 , Jerrold M Olefsky 5 , Wenxian Fu 6
Wei Ying 1 , Yun Sok Lee 1 , Yi Dong 2 , Jason S Seidman 3 , Meixiang Yang 4 , Roi Isaac 1 , Jong Bae Seo 1 , Bi-Huei Yang 2 , Joshua Wollam 1 , Matthew Riopel 1 , Joanne McNelis 1 , Christopher K Glass 3 , Jerrold M Olefsky 5 , Wenxian Fu 6
+ et al

[No authors listed]

Author information
  • 1 Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 2 Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 3 Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 4 Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; The First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China.
  • 5 Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: jolefsky@ucsd.edu.
  • 6 Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: w3fu@ucsd.edu.

摘要


The nature of obesity-associated islet inflammation and its impact on β cell abnormalities remains poorly defined. Here, we explore immune cell components of islet inflammation and define their roles in regulating β 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 intra-islet macrophages, independent of recruitment from circulating monocytes. Functionally, intra-islet macrophages impair β cell function in a cell-cell contact-dependent manner. Increased engulfment of β 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 β cell proliferation in a PDGFR signaling-dependent manner. Together, these data define distinct roles and mechanisms for islet macrophages in the regulation of islet β cells.

KEYWORDS: islet inflammation, local macrophages proliferation, macrophages, obesity, β cell function, β cell proliferation