Abstracts - Orals, Featured Poster Presentations, and Posters
FP33-Insulin Signaling & Inflammation
Presentation Start Time: 10:55 AM
Room 303 (Moscone Center)
Poster Board MON-844
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
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