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

113 Citations (Scopus)

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

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Complement Factor D
Adipokines
Medical problems
Type 2 Diabetes Mellitus
Insulin
Hyperglycemia
Glucose
Cell Physiological Phenomena
Glucose Intolerance
Physiology
Adipocytes
Respiration
Animals
Adenosine Triphosphate
Switches
Peptides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lo, J. C., Ljubicic, S., Leibiger, B., Kern, M., Leibiger, I. B., Moede, T., ... 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

Adipsin is an adipokine that improves β cell function in diabetes. / Lo, James C.; Ljubicic, Sanda; Leibiger, Barbara; Kern, Matthias; Leibiger, Ingo B.; Moede, Tilo; Kelly, Molly E.; Chatterjee Bhowmick, Diti; Murano, Incoronata; Cohen, Paul; Banks, Alexander S.; Khandekar, Melin J.; Dietrich, Arne; Flier, Jeffrey S.; Cinti, Saverio; Blüher, Matthias; Danial, Nika N.; Berggren, Per Olof; Spiegelman, Bruce M.

In: Cell, Vol. 158, No. 1, 03.07.2014, p. 41-53.

Research output: Contribution to journalArticle

Lo, JC, Ljubicic, S, Leibiger, B, Kern, M, Leibiger, IB, Moede, T, Kelly, ME, Chatterjee Bhowmick, D, Murano, I, Cohen, P, Banks, AS, Khandekar, MJ, Dietrich, A, Flier, JS, Cinti, S, Blüher, M, Danial, NN, Berggren, PO & Spiegelman, BM 2014, 'Adipsin is an adipokine that improves β cell function in diabetes', Cell, vol. 158, no. 1, pp. 41-53. https://doi.org/10.1016/j.cell.2014.06.005
Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T et al. Adipsin is an adipokine that improves β cell function in diabetes. Cell. 2014 Jul 3;158(1):41-53. https://doi.org/10.1016/j.cell.2014.06.005
Lo, James C. ; Ljubicic, Sanda ; Leibiger, Barbara ; Kern, Matthias ; Leibiger, Ingo B. ; Moede, Tilo ; Kelly, Molly E. ; Chatterjee Bhowmick, Diti ; Murano, Incoronata ; Cohen, Paul ; Banks, Alexander S. ; Khandekar, Melin J. ; Dietrich, Arne ; Flier, Jeffrey S. ; Cinti, Saverio ; Blüher, Matthias ; Danial, Nika N. ; Berggren, Per Olof ; Spiegelman, Bruce M. / Adipsin is an adipokine that improves β cell function in diabetes. In: Cell. 2014 ; Vol. 158, No. 1. pp. 41-53.
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