Evidence that abscissic acid participates in the response to hyperglycemia in humans
P. Ameri1, S. Bruzzone1, L. Briatore1, E. Mannino2, G. Basile1, M. Ponta1, A. Grozio1, M. Magnone1, L. Guida1, S. Scarfi1, A. Salis1, G. Damonte1, L. Sturla1, A. Nencioni1, D. Fenoglio1, F. Fiory2, C. Miele2, F. Beguinot2, D. Maggi1, R. Cordera1, G. Murialdo1, A. De Flora1 & E. Zocchi1
Abscissic acid (ABA) is a hormone best known for its role in plants. We previously showed that it is released by pancreatic beta-cells upon glucose stimulation, and autocrinally enhances insulin secretion.
Here we additionally report that ABA promotes glucose uptake by rat L6 myoblasts and murine 3T3-L1 cells differentiated to adipocytes, at least partly by inducing GLUT-4 translocation to the plasma membrane.
To determine whether ABA is involved in the response to hyperglycemia in vivo, we assessed its plasma concentrations (ABAp) in eight healthy volunteers and eight type 2 diabetes mellitus (T2DM) patients during an oral glucose tolerance test (OGTT). In healthy subjects, ABAp increased two to ninefold over basal values, starting 1560 min after glucose administration. There was a significant positive correlation between ABA and glucose areas under the curve (AUC) (r 0.905, P <0.01). In contrast, ABAp did not increase during OGTT in T2DM patients. An intravenous GTT (IVGTT) was also performed in six of the eight volunteers. Only two showed an increase in ABAp similar to that observed during OGTT. Overall, median and range ABAp AUC were lower during IVGTT than OGTT.
In rat insulinoma cells INS-1 and human pancreatic islets, GLP-1 potentiated ABA secretion by ~10 and 2 times in low- and high-glucose respectively (P<0.01), an effect abrogated by silencing of the GLP-1 receptor.
Beta-cells are likely the major source of circulating ABA, since fasting ABAp was significantly lower in seven type 1 DM patients (0.17±0.10 nM) than in 25 healthy subjects (1.51±1.29 nM, P <0.01) and in 21 T2DM patients (1.45±1.30 nM, P<0.01). However, human adipose tissue also released ABA when incubated with glucose.
In conclusion, our results suggest that ABA is a new hormone involved in glucose metabolism and particularly in the incretin response to oral glucose in humans.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.