Chemerin regulates β-cell function in mice

Sci Rep. 2011;1:123. doi: 10.1038/srep00123. Epub 2011 Oct 19.

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.

MeSH terms

  • Adipose Tissue / pathology
  • Adipose Tissue / physiopathology
  • Animals
  • Cell Line
  • Chemokines
  • Chemotactic Factors / antagonists & inhibitors
  • Chemotactic Factors / deficiency
  • Chemotactic Factors / genetics
  • Chemotactic Factors / physiology*
  • Diet, High-Fat / adverse effects
  • Gene Knockdown Techniques
  • Glucose Tolerance Test
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Macrophages / pathology
  • Maf Transcription Factors, Large / genetics
  • Maf Transcription Factors, Large / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • CMKLR1 protein, mouse
  • Chemokines
  • Chemotactic Factors
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Maf Transcription Factors, Large
  • Mafa protein, mouse
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled
  • chemerin protein, mouse