title: Sitagliptin: anti-platelet effect in diabetes and healthy volunteers.
abstract: Sitagliptin, a selective dipeptidyl peptidase-4 inhibitor drug is used to treat type-2 diabetes (T2DM). We investigated the anti-platelet activity of sitagliptin in patients with T2DM and in in vitro samples obtained from healthy humans. Patients with T2DM (27 male + 23 female) were selected and followed up before (control) and after treatment with sitagliptin for up to 3 months. Platelets were isolated from the blood of sitagliptin treated patients and controls. Patients with T2DM treated with sitagliptin for 1and 3 months, showed 10 ± 2% and 30 ± 5% inhibition of platelet aggregation, respectively. For the in vitro study, platelets from 10 normal humans (n = 10) were isolated. Platelet aggregation, intracellular free calcium and tyrosine phosphorylation of multiple proteins were measured by aggregometer, spectrofluorometer and western blotting, respectively. Platelets pre-treated with 5 and 10 µg/ml of sitagliptin, showed 25 ± 4% and 40 ± 6% inhibition of thrombin-induced platelet aggregation, respectively. Sitagliptin decreased intracellular free calcium (2.5-fold) and tyrosine phosphorylation of multiple proteins in thrombin-induced platelet activation. Sitagliptin inhibited platelet aggregation in T2DM as well as in healthy humans. Sitagliptin has significant concentration-dependent anti-platelet activity. This activity was due to its inhibitory effect on intracellular free calcium and tyrosine phosphorylation.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Gupta
authors.forename: Akhilesh Kumar
authors.initials: AK
authors.lastname: Verma
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Kailashiya
authors.forename: Surya Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Narender
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D013917:Thrombin / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014443:Tyrosine / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D014230:Triazoles; D014443:Tyrosine; D013917:Thrombin; D002118:Calcium; D000068900:Sitagliptin Phosphate