Glucagon as a determinant of fibrinolytic activity in men with different stages of glucose tolerance: impact of glucagon on fibrinolysis

Abstract

Glucagon plays an important role in postprandial hyperglycemia in type 2 diabetes (T2DM), and coexists with insulin resistance and impaired fibrinolysis. We analyzed the response of plasminogen activator inhibitor-1 (PAI-1) to a lipid-glucose-protein test and the relationship between glucagon and PAI-1, tissue plasminogen activator (t-PA) and PAI-1/t-PA in 26 men with normal glucose tolerance (NGT), nine with impaired glucose tolerance (IGT) and 12 with T2DM. Fasting and postprandial PAI-1 were higher in T2DM versus NGT (P < 0.05). In univariate analysis in NGT, fasting and area under the curve (AUC) PAI-1 showed a strong relationship with fasting (P = 0.003, P = 0.006) and postprandial (P = 0.041, P = 0.045) glucagon, t-PA with fasting glucagon (P = 0.014), and PAI-1/t-PA with fasting (P = 0.047) and AUC glucagon (P = 0.017). In IGT fasting, AUC PAI-1 and PAI-1/t-PA were associated with AUC glucagon (P = 0.035, P = 0.032, P = 0.023). In NGT with the fasting metabolic parameters and insulin resistance as independent variables, fasting glucagon remained an independent covariate for PAI-1 and PAI-1/t-PA. In another model, postprandial glucagon was independently associated with PAI-1/t-PA in NGT (P < 0.05). Besides the already established determinants, we found an independent association between glucagon and fibrinolysis in NGT. Further studies are needed to identify the link between glucagon, insulin resistance and hemostasis.