The GenoDiabMar Registry: A Collaborative Research Platform of Type 2 Diabetes Patients.

The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort.

Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes.

Disintegrin and metalloproteinase domain 17 (ADAM17) activates inflammatory and fibrotic processes through the shedding of various molecules such as Tumor Necrosis Factor-α (TNF-α) or Transforming Growht Factor-α (TGF-α). There is a well-recognised link between TNF-α, obesity, inflammation, and diabetes. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium.

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes.

Acute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how deletion in proximal tubules affects different renal structures in an obese mice model.

SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients.

Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines.

Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy.

ADAM17 is a disintegrin and metalloproteinase capable of cleaving the ectodomains of a diverse variety of molecules including TNF-α, TGF-α, L-selectin, and ACE2. We have previously demonstrated that renal ADAM17 is upregulated in diabetic mice. The role of endothelial () and proximal tubular () deletion in renal histology, modulation of the renin angiotensin system (RAS), renal inflammation, and fibrosis was studied in a mouse model of type 1 Diabetes Mellitus.

Angiotensin-converting enzyme 2 influences pancreatic and renal function in diabetic mice.

Type 1 diabetes is a T-cell mediated autoimmune disease characterized by pancreatic beta cells destruction. Angiotensin-converting enzyme 2 (ACE2), a component of renin-angiotensin system (RAS) has been identified in pancreas from type 2 diabetic mice and its overexpression prevents beta cell dysfunction. We studied the effect of ACE2 deletion on pancreatic and renal function in the nonobese diabetic mice, a model that mimics type 1 diabetes.

Role of ADAM17 in kidney disease.

It is known that the renin-angiotensin system plays a major role in the pathophysiology of cardiovascular disease and renal injury. Within the renin-angiotensin system, angiotensin-converting enzyme 2 (ACE2) cleaves ANG II to generate ANG(1-7) peptide, which counteracts the adverse effects of ANG II accumulation. ACE2 can undergo cleavage or shedding to release the catalytically active ectodomain into the circulation by a disintegrin and metalloprotease (ADAM)17, also known as TNF-α-converting enzyme.

Circulating ADAMs are associated with renal and cardiovascular outcomes in chronic kidney disease patients.

Background: A disintegrin and metalloproteinase (ADAM) 17, also known as tumour necrosis factor α-converting enzyme (TACE), is a metalloproteinase that releases the ectodomains of most growth factors, cytokines, receptors and enzymes and has been associated with the presence of chronic kidney disease (CKD) and cardiovascular (CV) disease. The role of circulating ADAMs in the progression of renal function and CV events in CKD patients is unknown.

Methods: A total of 2570 subjects from an observational and multicentre study with CKD Stages 3-5, CKD Stage 5D and controls without any history of CV disease were studied.

Sex dimorphism in ANGII-mediated crosstalk between ACE2 and ACE in diabetic nephropathy.

Angiotensin-converting enzyme (ACE) and ACE2 play a critical role in the renin-angiotensin system (RAS) by altering angiotensin II (ANGII) levels, thus governing its deleterious effects. Both enzymes are altered by sex and diabetes, and play an important role in the development of diabetic nephropathy (DN). Importantly, previous evidence in diabetic and ACE2-deficient (ACE2KO) males suggest a sex-dependent crosstalk between renal ACE and ACE2.

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse.

Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model.