FP13-5 Glucagon-Like Peptide-1 Analogue Therapy Impacts Inflammatory Macrophages & Cytokine– Increasing Evidence for It's Anti-Inflammatory Actions

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP13-GI Peptides, Beta Cells & Glycemia
Translational
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:20 AM
Room 304 (Moscone Center)

Poster Board SAT-838
Andrew E Hogan*1, Lydia Lynch2, Gadintshware Gaoatswe3, Conor Woods3, Ruaidhri Jackson4, Jean M O'Connell5, Paul N Moynagh4 and Donal O'Shea3
1National Children's Research Centre, Dublin, Ireland, 2Harvard Medical School, Boston, MA, 3St Vincent's University Hospital, Dublin, Ireland, 4National University of Ireland Maynooth, Ireland, 5St Vincent's University Hosp, Dublin 4, Ireland
Glucagon-like peptide 1 (GLP-1) is a gut hormone used in the treatment of type 2 diabetes mellitus (T2DM). There is emerging evidence that GLP-1 has anti-inflammatory activity, with clinical impact in chronic inflammatory conditions such as obesity and psoriasis. We hypothesized that GLP-1 would positively impact on inflammation and macrophage polarization in human T2DM.  We studied a cohort of obese T2DM patients before and 8 weeks after starting GLP-1 analogue therapy. We found that soluble CD163, a molecule released from inflammatory macrophage activation, was significantly higher in the T2DM cohort compared to healthy controls, and was reduced by GLP-1 analogue therapy (220 ng/ml vs. 171 ng/ml, p<0.001) independent of reduction in HbA1c. GLP-1 therapy-induced reduction of inflammatory M1 macrophages (F480+ CD11b+ CD11c+) was confirmed in a murine model of diet-induced obesity (11.2% vs. 6.8%, p<0.05). GLP-1 analogue therapy in the cohort of T2DM patients resulted in a reduction in the basal levels of the inflammatory cytokines TNF-alpha (264 pg/ml vs. 149 pg/ml, p<0.05) and IL-6 (1300 pg/ml vs. 461 pg/ml, p<0.05) and an increase in the “anti-inflammatory” adipokine, adiponectin (4100 pg/ml vs. 5,594 pg/ml, p<0.01). This was paired with an increase in stimulated PBMC response (TNF-alpha (939 pg/ml vs. 3,488 pg/ml p<0.05) and IL-6 (4,007 pg/ml vs. 8,560 pg/ml p<0.05)) via restoration of the immune signalling pathway, NFkB. Our results indicate that GLP-1 is impacting innate immunity and provides mechanistic rationale for its emerging use beyond the current indications of diabetes to other inflammatory diseases.

Nothing to Disclose: AEH, LL, GG, CW, RJ, JMO, PNM, DO

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