Search results for "dipeptidyl"
showing 10 items of 54 documents
Type-II transmembrane prolyl dipeptidases and matrix metalloproteinases in membrane vesicles of active endothelial cells.
2006
Conclusions: Endothelia cells in sparse culture are migratory and increase the production of gelatinases of serine- and metallo-classes in membrane vesicles. Collectively, proteases associated with membrane vesicles degrade extracellular matrix components including type-I and type-IV collagens, laminin and fibronectin. Inhibitor studies suggest the existence of small gelatinases that were derived from these serine- and metallo-proteases. Thus, further studies are warranted to demonstrate the cooperative action of metallo- and serine proteases on cell surfaces and in extracellular vesicles during endothelial cell migration in 3D collagenous matrices, and potential proteolytic activation mech…
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…
Weight response to GLP-1 receptor agonists: Why women do it better?
2022
nessuno
The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
2021
Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiati…
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…
A Decision Support Tool for Appropriate Glucose-Lowering Therapy in Patients with Type 2 Diabetes
2015
Contains fulltext : 152084.pdf (Publisher’s version ) (Open Access) BACKGROUND: Optimal glucose-lowering therapy in type 2 diabetes mellitus requires a patient-specific approach. Although a good framework, current guidelines are insufficiently detailed to address the different phenotypes and individual needs of patients seen in daily practice. We developed a patient-specific decision support tool based on a systematic analysis of expert opinion. MATERIALS AND METHODS: Based on the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) 2012 position statement, a panel of 12 European experts rated the appropriateness (RAND/UCLA Appropriateness Method) of tre…