title: 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.
authors.affiliation: Centre for Clinical Studies-Metabolism and Endocrinology, GWT TU Dresden, Technical University Dresden, Fiedlerstrasse 34, D-01307 Dresden, Germany. henkel@gwtonline-zks.de
authors.forename: Elena
authors.initials: E
authors.lastname: Henkel
authors.forename: Sarsta
authors.initials: S
authors.lastname: Gallo
authors.forename: Gilvina
authors.initials: G
authors.lastname: Siegert
authors.forename: Cabriele
authors.initials: C
authors.lastname: Koehler
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
mesh_terms: D000368:Aged; D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D005934:Glucagon / Q000097:blood* / Q000378:metabolism*; D018149:Glucose Intolerance / Q000097:blood* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000502:physiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D005934:Glucagon; D010959:Tissue Plasminogen Activator