Adipsin is an adipokine that improves β cell function in diabetes

James C. Lo, Sanda Ljubicic, Barbara Leibiger, Matthias Kern, Ingo B. Leibiger, Tilo Moede, Molly E. Kelly, Diti Chatterjee Bhowmick, Incoronata Murano, Paul Cohen, Alexander S. Banks, Melin J. Khandekar, Arne Dietrich, Jeffrey S. Flier, Saverio Cinti, Matthias Blüher, Nika N. Danial, Per Olof Berggren, Bruce M. Spiegelman

Research output: Contribution to journalArticle

135 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)41-53
Number of pages13
JournalCell
Volume158
Issue number1
DOIs
StatePublished - Jul 3 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lo, J. C., Ljubicic, S., Leibiger, B., Kern, M., Leibiger, I. B., Moede, T., Kelly, M. E., Chatterjee Bhowmick, D., Murano, I., Cohen, P., Banks, A. S., Khandekar, M. J., Dietrich, A., Flier, J. S., Cinti, S., Blüher, M., Danial, N. N., Berggren, P. O., & Spiegelman, B. M. (2014). Adipsin is an adipokine that improves β cell function in diabetes. Cell, 158(1), 41-53. https://doi.org/10.1016/j.cell.2014.06.005