Schematic of Experimental Protocols. Protocols were comprised of pretreatment and measurement periods. Pretreatment involved perfusion with the test mediator for 30 minutes (gray bar) prior to systemic injection of LPS (arrow). Microvascular Permeability (Lp) measurements (black bar) began 15 minutes after LPS injection.

FIG 3A. The effect of GLP-1 on the increase in L_p induced by LPS. Illustrated are the continuous effects of perfusion with GLP-1 (solid line) compared to the effect of LPS alone (large dashed line) and LPS plus GLP-1 (small dashed line). GLP-1 attenuated the increase in microvascular permeability induced by LPS. *Significant difference in L_p between LPS alone and LPS plus GLP-1 (p < 0.05). Data is shown as mean L_p ± SEM × 10⁻⁷ cm/s⁻¹/cmH₂O⁻¹.
FIG 3B. The effect of GLP-1 on the increase in L_p induced by LPS. Data are represented as the area under the curve (AUC) of L_p over time. LPS alone increased L_p 2-fold over baseline. Subsequent perfusion with GLP-1 reduced this increase in L_p by 75%. *Significant difference from baseline (p<0.0001). #Significant difference from LPS alone (p<0.0001). Data is shown as mean AUC ± SEM.

FIG 5A. Inhibition of cAMP synthesis reduces the effect of GLP-1 on L_p. Illustrated are the continuous effects of perfusion with LPS (large dashed line) compared to the effect of LPS+GLP-1 (small dashed line) and LPS+GLP-1+ a cAMP synthesis inhibitor (solid line). Perfusion of a cAMP synthesis inhibitor reduced the effect of GLP-1 on the LPS-induced increase in L_p. *Significant difference in L_p between LPS+GLP-1 and LPS+GLP-1+cAMP synthesis inhibitor (p < 0.05). Data is shown as mean L_p ± SEM × 10⁻⁷ cm/s⁻¹/cmH₂O⁻¹.
FIG 5B. Inhibition of cAMP degradation enhances the effect of GLP-1 on L_p. Illustrated are the continuous effects of perfusion with LPS (large dashed line) compared to the effect of LPS+GLP-1 (small dashed line) and LPS+GLP-1+ a cAMP degradation inhibitor (solid line). Perfusion of a cAMP degradation inhibitor enhanced the effect of GLP-1 on the LPS-induced increase in L_p. *Significant difference in L_p between LPS+GLP-1 and LPS+GLP-1+cAMP degradation Inhibitor (p < 0.05). Data is shown as mean L_p ± SEM × 10–7 cm/s⁻¹/cmH₂O⁻¹.
FIG 5C. Inhibition of PKA eliminates the effect of GLP-1 on L_p. Illustrated are the continuous effects of perfusion with LPS (large dashed line) compared to the effect of LPS+GLP-1 (small dashed line) and LPS+GLP-1+ a PKA inhibitor (solid line). Perfusion of a PKA inhibitor completely blocked the effect of GLP-1 on the LPS-induced increase in L_p . *Significant difference in L_p between LPS+GLP-1 and LPS+GLP-1+PKA inhibitor (p < 0.05). Data is shown as mean L_p ± SEM × 10–7 cm/^s−1/cmH₂O⁻¹.
FIG 5D. The involvement of the cAMP/PKA Pathway in the effect of GLP-1 on L_p. Data are represented as the area under the curve (AUC) of L_p over time. Perfusion of a cAMP synthesis inhibitor and a PKA inhibitor blocked the effect of GLP-1 on the LPS-induced increase in L_p by 60% and 100%, respectively. *Significant difference from LPS alone (p<0.001). #Significant difference from LPS plus GLP-1 (p<0.0001). Data is shown as mean AUC ± SEM.

The dose response of GLP-1 on basal L_p. Illustrated is the continuous effect of perfusion with GLP-1 at 50 μmol/L, 5 μmol/L, and 0.5 μmol/L on basal L_p. After 5 minutes of infusion, GLP-1 did not increase baseline L_p at any dose. *Significant difference in L_p between GLP-1 dose and basal L_p. Data is shown as mean L_p ± SEM × 10⁻⁷ cm/s⁻¹/cmH₂O⁻¹.

FIG 4A. The involvement of the GLP-1 receptor in the effect of GLP-1 on L_p. Illustrated are the continuous effects of perfusion with LPS (large dashed line) compared to the effect of LPS+GLP-1 (small dashed line) and LPS+GLP-1+ a GLP-1 receptor inhibitor (solid line). Perfusion of a GLP-1 receptor inhibitor reduced the effect of GLP-1 on the LPS-induced increase in L_p . *Significant difference in L_p between LPS+GLP-1 and LPS+GLP-1+GLP-1 Receptor Inhibitor (p < 0.05). Data is shown as mean L_p ± SEM × 10⁻⁷ cm/s⁻¹/cmH₂O⁻¹.
FIG 4B. The involvement of the GLP-1 receptor in the effect of GLP-1 on L_p. Data are represented as the area under the curve (AUC) of L_p over time. Perfusion of a specific GLP-1 receptor antagonist attenuated the effect of GLP-1 on the LPS-induced increase in L_p by 60%. *Significant difference from LPS alone (p<0.001). #Significant difference from LPS plus GLP-1 (p<0.0001). Data is shown as mean AUC ± SEM.