Vitamin C further improves the protective effect of GLP-1 on the ischemia-reperfusion-like effect induced by hyperglycemia post-hypoglycemia in type 1 diabetes

Abstract

BackgroundIt has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested.Methods15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured.ResultsAfter 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia.ConclusionsThis study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.

The protective effect of the Mediterranean diet on endothelial resistance to GLP-1 in type 2 diabetes: a preliminary report

“…Therefore, it has been suggested that hyperglycemia induces such a GLP-1 resistance, mainly through the generation of an oxidative stress [10]. This hypothesis has been confirmed in vivo showing that the GLP-1 action can be improved by an antioxidant, vitamin C [12,13]. The results of the present study, in our opinion, not only confirm this finding, but may also have a significant clinical impact.…”

“…Consistently, GLP-1 has demonstrated to improve endothelial function in diabetes [ 9 , 10 ], possibly increasing the antioxidant defenses of the endothelium [ 11 ] and decreasing oxidative stress generation [ 10 ]. However, it is worth mentioning that, in both type 1 and type 2 diabetes, hyperglycemia induces an endothelial resistance to the action of GLP-1, with oxidative stress serving as the mediator of this phenomenon [ 10 , 12 , 13 ].…”

Does Glucagon-like Peptide-1 Ameliorate Oxidative Stress in Diabetes? Evidence Based on Experimental and Clinical Studies

“…This can be contributed to different actions of vitamin C and GLP-1, vitamin C being a scavenger of ROS and GLP-1 acting through induction of intracellular antioxidant defenses, respectively. Similar results were obtained in T1D patients in a study of effects of GLP-1 and/or vitamin C on the glycemic changes during I/R like conditions, where hypoglycemic conditions were followed by either normo- or hyperglycemia [157]. During hypoglycemia, levels of both 8-iso-PGF 2α and nitrotyrosine increased, and these levels increased even more when hyperglycemia replaced hypoglycemia as compared to normoglycemia.…”

Effects of exenatide on postprandial vascular endothelial dysfunction in type 2 diabetes mellitus

“…Second, the direct effect of GLP-1 on inflammatory cytokines, adhesion factors, oxidative stress factors, among others, and their effects on vascular endothelial function, was not evaluated in this study. Since GLP-1 formulations are known to suppress oxidative stress and inflammation and thus suppress vascular endothelial dysfunction [ 34 ]. Our results showed that improvement in postprandial hypertriglyceridemia was responsible for 41% improvement in postprandial vascular endothelial function, while the remaining 59% was probably related to the direct effect of GLP-1 on vascular endothelial function.…”