title: Different modulation of dipeptidyl peptidase-4 activity between microvascular and macrovascular human endothelial cells.
abstract: Dipeptidyl peptidase 4 (DPP-4) is an enzyme that is produced by endothelial cells in different districts and circulates in plasma. Patients with type 2 diabetes show a reduction in active Glucagon-Like Peptide-1 (GLP-1) that could be due to impairment of secretion or its degradation or both. GLP-1 is rapidly inactivated in vivo, mainly by the DPP-4. Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity. In order to better elucidate the role of insulin sensitizers on the modulation of GLP-1 circulating levels, DPP-4 activity and mRNA expression were measured in cultured human aortic endothelial cells (HAEC) and human microvascular dermal endothelial cells (HMVEC) exposed to high glucose, Metformin and Rosiglitazone. Present data show that hyperglycemia is capable of increasing in a significant manner the DPP-4 activity only in microvascular endothelial cells. Rosiglitazone is able to modulate in a negative manner the expression of DPP-4 but not its activity in macrovascular endothelial cells, while at 24 h of exposure it is able to increase significantly DPP-4 activity but not its expression in microvascular endothelial cells. Metformin at 48 h only in microvascular endothelial cells is able to reduce in a significant manner (p = 0.01) the activity of DPP-4 but not its expression. The modulation of DPP-4 is site specific.
authors.affiliation: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pala
authors.forename: Anna
authors.initials: A
authors.lastname: Pezzatini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dicembrini
authors.forename: Silvia
authors.initials: S
authors.lastname: Ciani
authors.forename: Stefania
authors.initials: S
authors.lastname: Gelmini
authors.forename: Barbara Gabriella
authors.initials: BG
authors.lastname: Vannelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Cresci
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Rotella
mesh_terms: D001011:Aorta / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D020405:Dermis / Q000098:blood supply; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D055806:Microvessels; D009928:Organ Specificity
chemical_list: D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4