Glucagon-Like Peptide-1 Is Increased In Blood Plasma and May Play Neuroprotective Roles After Ischemic Stroke In Human

Introduction: Glucagon-like peptide-1 (GLP-1) is an incretin peptide, which is secreted by intestinal L-cells after food intake and increases the insulin secretion in a glucose-dependent manner. Increasing evidence indicates that GLP-1 may play neuroprotective roles in animal stroke models; however, there have been few reports regarding the relationship between GLP-1 and stroke in human. Hypothesis: GLP-1 is increased in plasma and plays neuroprotective roles after ischemic stroke in human. Methods: We prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy controls. We measured GLP-1 in fasting blood plasma at five time points after the onset (days 0, 3, 7, 14 and 90) and investigated clinical information in the stroke patients. Results: Average GLP-1 values at day 0 were significantly higher in the stroke patients than the controls (2.7 ± 0.4 vs. 1.5 ± 0.2 pmol/L, p = 0.0107). In the patients, GLP-1 values at day 0 tended to be negatively associated with neurological severity as evaluated by National Institute of Health Stroke Scale (NIHSS) on admission (r = - 0.1264, p = 0.0565). Moreover, when the stroke patients were divided into 4 groups (Q1, Q2, Q3 and Q4 from milder to severer) according to the interquartile range of the NIHSS, Q1 (3.6 ± 0.9 pmol/L, p = 0.0014) and Q2 (2.6 ± 0.7 pmol/L, p = 0.0429) groups had significantly higher GLP-1 values than the controls (Figure). GLP-1 continued to be increased until the 90 days after the onset, compared to that of the controls (day 0 (2.7 ± 0.4 pmol/L, p = 0.0107), day 3 (6.0 ± 0.4, p < 0.0001), day7 (7.1 ± 0.6, p < 0.0001), day 14 (8.3 ± 0.8, p < 0.0001), day 90 (8.3 ± 0.7, p < 0.0001)). GLP-1 values tended to be higher in the good outcome group (modified Rankin Scale (mRS) ≤ 1 at 90 day) than the poor outcome group (mRS ≥ 2). Conclusions: GLP-1 is increased in blood plasma after ischemic stroke in human. The increase in the acute phase may be associated with the reduction of neurological severity in ischemic stroke.