Vala Hamidi

Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy.

Mechanisms underlying anti-diabetic effects of GLP1 analogs remain incompletely understood. We observed that in prediabetic humans exenatide treatment acutely induces interleukin-6 (IL-6) secretion by monocytes and IL-6 in systemic circulation. We hypothesized that GLP1 analogs signal through IL-6 in adipose tissue (AT) and used the mouse model to test if IL-6 receptor (IL-6R) signaling underlies the effects of the GLP1-IL-6 axis.

(A) Mouse immortalized brown pre-adipocytes seeded at confluency were induced for brown adipogenesis in DMEM/10% fetal bovine serum (FBS) medium containing 50 nM insulin/0.5 mM IBMX, 1 μM dexamethasone, 1 nM 3,5,3′-Triiodothyronine (T3), and 5 μM rosiglitazone for 24 h, were washed and cultured in DMEM/10% FBS medium containing 500 pg/mL mouse IL-6, 100 nM liraglutide, or their combination, for 6 and 24 h. UCP1 expression was measured by western blotting. Arrow: UCP1; ns, nonspecific band.