Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice

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Li, P., Lu, M., Nguyen, M.T., Bae, E., Chapman, J., Feng, D., Hawkins, M., Pessin, J.E., Sears, D.D., Nguyen, A.K., Amidi, A., Watkins, S.M., Nguyen, U., Olefsky, J.M.

  • J Biol Chem
  • 2010
  • 5.486
  • 3(113):ra19.
  • Human,Mouse,Non-Human Primate,Rat
  • MSD
  • Epididymal White Adipose Tissue lysates
  • 免疫/内分泌
  • 巨噬细胞
  • 肥胖
  • IL-10, IL-12 p70, IL-6




Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP(3)R and is enriched in pancreatic beta cells. We found that ankyrin-B-deficient islets displayed impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular Ca2+ release, and reduced the abundance of IP3R. Ankyrin-B-haploinsufficient mice exhibited hyperglycemia after oral ingestion but not after intraperitoneal injection of glucose, consistent with impaired parasympathetic potentiation of glucose-stimulated insulin secretion. The R1788W mutation of ankyrin-B impaired its function in pancreatic islets and is associated with type 2 diabetes in Caucasians and Hispanics. Thus, defective glycemic regulation through loss of ankyrin-B-dependent stabilization of IP3R is a potential risk factor for type 2 diabetes.
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