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

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.

• Authors: 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
• Journal: Cell (Cell) Vol. 158 Issue 1 Pg. 41-53 (Jul 03 2014) ISSN: 1097-4172 [Electronic] United States
• PMID: 24995977 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Insulin
• Complement C3a
• CFD protein, human
• Complement Factor D
• complement factor D, mouse
• Glucose

Topics

• Adipose Tissue (metabolism)
• Animals
• Complement C3a (metabolism)
• Complement Factor D (genetics, metabolism)
• Diabetes Mellitus, Type 2 (metabolism, physiopathology)
• Diet, High-Fat
• Glucose (metabolism)
• Humans
• Inflammation (metabolism)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (metabolism)
• Mice