Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Acta Diabetol. 2012 Dec;49 Suppl 1:S59-63. doi: 10.1007/s00592-010-0195-3. Epub 2010 May 9.
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.
二肽基肽酶 4（DPP-4）是一种在不同部位产生的酶，存在于血浆中循环。2 型糖尿病患者表现出活性胰高血糖素样肽-1（GLP-1）减少，这可能是由于分泌受损或其降解或两者兼而有之。GLP-1在体内迅速失活，主要是通过 DPP-4。一些作者认为二甲双胍对 DPP-4 活性没有直接抑制作用，二甲双胍和其他双胍类药物增强 GLP-1 的分泌；其他作者则认为二甲双胍可能在抑制 DPP-4 活性方面发挥作用。为了更好地阐明胰岛素增敏剂对 GLP-1 循环水平调节的作用，在高糖、二甲双胍和罗格列酮作用下，测量了培养的人主动脉内皮细胞（HAEC）和人微血管真皮内皮细胞（HMVEC）中的 DPP-4 活性和 mRNA 表达。目前的数据表明，高血糖仅能显著增加微血管内皮细胞中 DPP-4 的活性。罗格列酮能够以负性方式调节 DPP-4 的表达，但不能调节其在大血管内皮细胞中的活性，而在暴露 24 小时后，它能够显著增加微血管内皮细胞中 DPP-4 的活性，但不能增加其表达。二甲双胍仅在暴露 48 小时后，能够显著降低（p = 0.01）微血管内皮细胞中 DPP-4 的活性，但不能降低其表达。DPP-4 的调节具有特定的部位特异性。
