title: Platelets from diabetic pigs exhibit hypersensitivity to thrombin.
abstract: Responses of platelets from diabetic and diabetic-hyperlipidemic pigs were studied. Pigs were made diabetic with single dose of alloxan, which acts by selectively destroying insulin-producing pancreatic beta cells thus inducing type 1 diabetes. Pigs were kept for 1 or 12 wk, during which thrombin-induced aggregation was monitored in washed platelets. The platelets showed increased sensitivity to aggregation within 1 wk of induction of diabetes. Hyperlipidemia alone for 12 wk did not increase platelet hypersensitivity, but hyperlipidemia together with diabetes significantly increased thrombin-induced platelet aggregation. Because this hypersensitivity occurred in washed platelets, this characteristic appears to be independent of any contribution by plasma factors or other blood cells. The hypersensitivity of platelets from diabetic pigs correlated with decreased activity of mitogen-activated protein kinase. These studies offer the first evidence that platelet hyperactivity occurs during the early stages (within a week) of induction of diabetes in pigs and before manifestation of other cardiovascular problems.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO, USA. shuklasd@missouri.edu
authors.forename: Shivendra D
authors.initials: SD
authors.lastname: Shukla
authors.forename: Sanjay V
authors.initials: SV
authors.lastname: Kansra
authors.forename: M A
authors.initials: MA
authors.lastname: Reddy
authors.forename: Sundeep M
authors.initials: SM
authors.lastname: Shukla
authors.forename: David M
authors.initials: DM
authors.lastname: Klachko
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000150:complications; D015536:Down-Regulation; D006949:Hyperlipidemias / Q000097:blood* / Q000150:complications; D020928:Mitogen-Activated Protein Kinases / Q000097:blood; D010974:Platelet Aggregation; D013552:Swine; D013917:Thrombin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin