title: Role of plasma kallikrein in diabetes and metabolism.
abstract: Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.
authors.affiliation: Edward P. Feener, PhD, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA, Tel.: +1 617 309 2599, Fax: +1 617 309 2637, E-mail: edward.feener@joslin.harvard.edu.
authors.forename: E P
authors.initials: EP
authors.lastname: Feener
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.forename: W
authors.initials: W
authors.lastname: Fickweiler
mesh_terms: D050156:Adipogenesis; D000818:Animals; D001777:Blood Coagulation; D001794:Blood Pressure; D001920:Bradykinin / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood*; D005174:Factor XII / Q000378:metabolism; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005947:Glucose / Q000378:metabolism; D006487:Hemostasis; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007249:Inflammation; D051379:Mice; D020842:Plasma Kallikrein / Q000502:physiology*; D011288:Prekallikrein / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism
chemical_list: D005174:Factor XII; D011288:Prekallikrein; D020842:Plasma Kallikrein; D005947:Glucose; D001920:Bradykinin