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Cell. 2014 Jul 3;158(1):41-53. doi: 10.1016/j.cell.2014.06.005.

Adipsin is an adipokine that improves β cell function in diabetes.

Author information

1
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
2
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 17176 Stockholm, Sweden.
4
Department of Medicine, University of Leipzig, Leipzig 04103, Germany.
5
Department of Experimental and Clinical Medicine, University of Ancona, 60020 Ancona, Italy.
6
Department of Surgery, University of Leipzig, Leipzig 04103, Germany.
7
Harvard Medical School, Boston, MA 02115, USA.
8
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bruce_spiegelman@dfci.harvard.edu.

Abstract

A hallmark of type 2 diabetes mellitus (T2DM) is the development of pancreatic β cell failure, which results in insulinopenia and hyperglycemia. We show that the adipokine adipsin has a beneficial role in maintaining β cell function. Animals genetically lacking adipsin have glucose intolerance due to insulinopenia; isolated islets from these mice have reduced glucose-stimulated insulin secretion. Replenishment of adipsin to diabetic mice treated hyperglycemia by boosting insulin secretion. We identify C3a, a peptide generated by adipsin, as a potent insulin secretagogue and show that the C3a receptor is required for these beneficial effects of adipsin. C3a acts on islets by augmenting ATP levels, respiration, and cytosolic free Ca(2+). Finally, we demonstrate that T2DM patients with β cell failure are deficient in adipsin. These findings indicate that the adipsin/C3a pathway connects adipocyte function to β cell physiology, and manipulation of this molecular switch may serve as a therapy in T2DM.

PMID:
24995977
PMCID:
PMC4128197
DOI:
10.1016/j.cell.2014.06.005
[Indexed for MEDLINE]
Free PMC Article

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