TY - JOUR
T1 - Adipsin Is an Adipokine that Improves β Cell Function in Diabetes
AU - Lo, James c.
AU - Ljubicic, Sanda
AU - Leibiger, Barbara
AU - Kern, Matthias
AU - Leibiger, Ingo b.
AU - Moede, Tilo
AU - Kelly, Molly e.
AU - Chatterjee Bhowmick, Diti
AU - Murano, Incoronata
AU - Cohen, Paul
AU - Banks, Alexander S.
AU - Khandekar, Melin j.
AU - Dietrich, Arne
AU - Flier, Jeffrey S.
AU - Cinti, Saverio
AU - Blüher, Matthias
AU - Danial, Nika N.
AU - Berggren, Per-Olof
AU - Spiegelman, Bruce m.
PY - 2014/7/3
Y1 - 2014/7/3
N2 - 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 Ca2+. 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.
AB - 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 Ca2+. 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.
UR - https://www.sciencedirect.com/science/article/pii/S0092867414007260
UR - https://pure.ulster.ac.uk/en/publications/adipsin-is-an-adipokine-that-improves-%CE%B2-cell-function-in-diabetes
U2 - 10.1016/j.cell.2014.06.005
DO - 10.1016/j.cell.2014.06.005
M3 - Article
SN - 0092-8674
VL - 158
SP - 41
EP - 53
JO - Cell
JF - Cell
IS - 1
ER -
