| First Author | Lo JC | Year | 2014 |
| Journal | Cell | Volume | 158 |
| Issue | 1 | Pages | 41-53 |
| PubMed ID | 24995977 | Mgi Jnum | J:214638 |
| Mgi Id | MGI:5603502 | Doi | 10.1016/j.cell.2014.06.005 |
| Citation | Lo JC, et al. (2014) Adipsin is an adipokine that improves beta cell function in diabetes. Cell 158(1):41-53 |
| abstractText | A hallmark of type 2 diabetes mellitus (T2DM) is the development of pancreatic beta cell failure, which results in insulinopenia and hyperglycemia. We show that the adipokine adipsin has a beneficial role in maintaining beta 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 beta cell failure are deficient in adipsin. These findings indicate that the adipsin/C3a pathway connects adipocyte function to beta cell physiology, and manipulation of this molecular switch may serve as a therapy in T2DM. |
