title: Chemerin regulates β-cell function in mice.
abstract: 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 β-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 β-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated β-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates β-cell function via maintaining MafA expression. These results indicate that chemerin regulates β-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. takahash@med.kobe-u.ac.jp
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Okimura
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suda
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.forename: Wakako
authors.initials: W
authors.lastname: Fujimoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Fyodor N
authors.initials: FN
authors.lastname: Zolotaryov
authors.forename: Kyoung Su
authors.initials: KS
authors.lastname: Hong
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.forename: Hidesuke
authors.initials: H
authors.lastname: Kaji
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000273:Adipose Tissue / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002460:Cell Line; D018925:Chemokines; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D055785:Gene Knockdown Techniques; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000473:pathology; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C486456:CMKLR1 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse