Search results for "Dipeptidyl peptidase"

Activation of EDTA-resistant Gelatinases in Malignant Human Tumors

2006

Abstract Among the many proteases associated with human cancer, seprase or fibroblast activation protein α, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remaine…

Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

2015

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular deat…

Incretin-Based Therapies Role in COVID-19 Era: Evolving Insights

2020

The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COV…

Seprase-DPPIV Association and Prolyl Peptidase and Gelatinase Activities of the Protease Complex

2005

Flavonoids against the SARS-CoV-2 induced inflammatory storm

2021

The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out …

Protease-mediated processing of Argonaute proteins controls small RNA association

2020

SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a cha…

Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes

2020

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by target…

Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors

2009

Type 2 diabetes is a chronic, progressive disease with a multi-faceted pathophysiology. Beyond the known defects of insulin resistance and beta-cell insufficiency, derangement of incretin hormones normally produced from the gut wall in response to food intake play an important role. In recent years, the 'incretin-based' therapies (IBTs) have been developed to address hyperglycemia through either mimicking the action of the endogenous incretin glucagon-like polypeptide (GLP-1) (GLP-1 receptor agonists) or by inhibiting the activity of the enzyme that degrades GLP-1 (the dipeptyl peptidase-4 inhibitors).We reviewed available evidence on the glucose lowering and anti-atherogenic effects of IBT…

Future perspectives of the pharmacological management of diabetic dyslipidemia

2019

Introduction: Diabetic dyslipidemia is frequent among patients with type 2 diabetes mellitus (T2DM) and is characterized by an increase in triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and small-dense (atherogenic) particles, and by a decrease in low high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 that are strongly related to insulin resistance. The increased flux of free fatty acids from adipose tissue to the liver aggravates hepatic insulin resistance and promotes all of aspects of the dyslipidemic state. Areas covered: Statins are the first-line agents for treatment while other lipid-lowering drugs (ezetimibe, fibrate and proprotein convertase…

Use of Novel Antidiabetic Agents in Patients with Type 2 Diabetes and COVID-19: A Critical Review

2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The latter is a pandemic that has the potential of developing into a severe illness manifesting as systemic inflammatory response syndrome, acute respiratory distress syndrome, multi-organ involvement and shock. In addition, advanced age and male sex and certain underlying health conditions, like type 2 diabetes mellitus (T2DM), predispose to a higher risk of greater COVID-19 severity and mortality. This calls for an urgent identification of antidiabetic agents associated with more favourable COVID-19 outcomes among patients with T2DM, as well as recognition of their potential underlying…