Chemerin regulates β-cell function in mice

Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 were expressed in beta-cell. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion (GSIS) in chemerin-deficient mice. Conversely, chemerin transgenic mice revealed enhanced GSIS and improved glucose tolerance. Expression of MafA, a pivotal transcriptional factor for beta-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated beta-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates beta-cell function via maintaining MafA expression. These results indicate that chemerin regulates beta-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.