FP33-3 Exenatide Increases Interleukin-1 Receptor Antagonist (IL1-RA) Concentration

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP33-Insulin Signaling & Inflammation
Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 303 (Moscone Center)

Poster Board MON-844
Paresh Dandona1, Husam Ghanim2, Kelly Green3, Sanaa Abuaysheh3, Sandeep S Dhindsa*4, Ajay Chaudhuri5, Antoine Makdissi6, Manav Batra3 and Reema A Patel7
1State Univ of NY, Buffalo, NY, 2Kaleida Health, Buffalo, NY, 3SUNY at Buffalo, 4SUNY at Buffalo, NY, 5SUNY at Buffalo, Williamsville, NY, 6State Univ of New York at Buffal, Buffalo, NY, 7SUNY Upstate Buffalo, Buffalo, NY
We have recently demonstrated that exenatide exerts a rapid and a potent anti-inflammatory effect including the suppression of IL-1β expression in peripheral blood mononuclear cells (MNC). Suppression of IL-1β secretion or activity has significant implications for insulin sensitivity and secretion and on glycemic control since it modulates the synthesis of SOCS-3 which interferes with insulin signaling and it mediates the inflammatory damage of the β-cell. We have now hypothesized that exenatide induces an increase in plasma concentrations of IL-1RA which is known to improve glycemia and β-cell function in type 2 diabetics. Twenty four obese type 2 diabetics were prospectively randomized to be injected subcutaneously with either exenatide 10 μg twice daily (n=12, mean age: 56 ±3 years; mean HbA1c:8.6±0.4%) or placebo twice daily (n=12, mean age: 54±4 years; mean HbA1c:8.5±0.3%) for 12 weeks. HbA1c fell by 0.5% while there was no change in body weight. IL-1β expression was suppressed by 22±10% in MNC, plasma concentration of IL-18 fell by 19% (from 546±58 to 436±46 pg/ml) while IL-1 RA concentrations increased significantly by 61±18% (from 318±53 to 456±88 pg/ml; p<0.05 for all). Exenatide also suppressed the mRNA expression in MNC of SOCS-3 and PTP-1B, two proteins that interfere with insulin signaling, by 31±10% and 18±5%, respectively. These modulators of inflammation and insulin signaling did not change in the placebo group. We conclude that exenatide induces an increase in IL-1RA concentrations in addition to suppressing IL-1β expression and plasma concentrations of IL-18. The combination of these effects would potentially be of benefit to both the integrity and function of the β-cell and insulin resistance.

Disclosure: PD: Advisory Group Member, Novo Nordisk, Advisory Group Member, Merck & Co.. Nothing to Disclose: HG, KG, SA, SSD, AC, AM, MB, RAP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm