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Ureteral stents are useful devices in urological surgery. The main objective of a ureteric stent is to allow passage of urine and reduce early or late complications related to obstruction in the urinary tract. Despite their widespread use, there is a general lack of knowledge and awareness in stent composition and indication of application. We represented a synthesis of our extensive research over materials, coatings and shapes available on the market and then analyzed the main characteristics and peculiarities of ureteral stents. We have also focused our attention over the side effects and complication that must be considered when placing a ureteral stent. Encrustation, microbial colonization, stent-related symptoms and patient's history must always be evaluated when there is the need for a ureteral stent. The perfect stent should have many characteristics including easy insertion and removal, easy manipulation, resistance to encrustation and migration, lack of complications, biocompatibility, radio-opacity, biodurability, affordability (cost-effectiveness), tolerability and optimal flow characteristics. Nevertheless, further research and studies need to be done to provide more information about stent composition and efficacy in vivo. In this narrative review, we covered the basic information and main characteristics of ureteral stents, in order to help clinicians choose the appropriate device needed for a given situation. [ABSTRACT FROM AUTHOR]

Key points: Afadin is a ubiquitously expressed scaffold protein with a recently discovered role in insulin signalling and glucose metabolism.Insulin‐stimulated phosphorylation of Afadin at S1795 occurs in insulin‐responsive tissues such as adipose tissue, muscle, liver, pancreas and heart.Afadin abundance and AfadinS1795 phosphorylation are dynamically regulated in metabolic tissues during diet‐induced obesity progression.Genetic silencing of AfadinS1795 phosphorylation improves glucose homeostasis in the early stages of diet‐induced metabolic dysregulation.AfadinS1795 phosphorylation contributes to the early development of obesity‐related complications in mice. Obesity is associated with systemic insulin resistance and numerous metabolic disorders. Yet, the mechanisms underlying impaired insulin action during obesity remain to be fully elucidated. Afadin is a multifunctional scaffold protein with the ability to modulate insulin action through its phosphorylation at S1795 in adipocytes. In the present study, we report that insulin‐stimulated AfadinS1795 phosphorylation is not restricted to adipose tissues, but is a common signalling event in insulin‐responsive tissues including muscle, liver, pancreas and heart. Furthermore, a dynamic regulation of Afadin abundance occurred during diet‐induced obesity progression, while its phosphorylation was progressively attenuated. To investigate the role of AfadinS1795 phosphorylation in the regulation of whole‐body metabolic homeostasis, we generated a phospho‐defective mouse model (Afadin SA) in which the Afadin phosphorylation site was silenced (S1795A) at the whole‐body level using CRISPR‐Cas9‐mediated gene editing. Metabolic characterization of these mice under basal physiological conditions or during a high‐fat diet (HFD) challenge revealed that preventing AfadinS1795 phosphorylation improved insulin sensitivity and glucose tolerance and increased liver glycogen storage in the early stage of diet‐induced metabolic dysregulation, without affecting body weight. Together, our findings reveal that AfadinS1795 phosphorylation in metabolic tissues is critical during obesity progression and contributes to promote systemic insulin resistance and glucose intolerance in the early phase of diet‐induced obesity. [ABSTRACT FROM AUTHOR]

The mechanism by which pancreas secretes high HCO3- has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO3- from serosa to mucosa or by moving H+ in the opposite direction. The aim of the present study was to determine whether H+/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition it may provide a protective pH buffer zone and K+ recirculation. Furthermore, it seems relevant to re-evaluate whether PPIs should be used in treatment therapies where pancreatic functions are already compromised. [ABSTRACT FROM AUTHOR]

Key Points: Afadin is a ubiquitously expressed scaffold protein with a recently discovered role in insulin signalling and glucose metabolism. Insulin-stimulated phosphorylation of Afadin at S1795 occurs in insulin-responsive tissues such as adipose tissue, muscle, liver, pancreas and heart. Afadin abundance and Afadin S1795 phosphorylation are dynamically regulated in metabolic tissues during diet-induced obesity progression. Genetic silencing of Afadin S1795 phosphorylation improves glucose homeostasis in the early stages of diet-induced metabolic dysregulation. Afadin S1795 phosphorylation contributes to the early development of obesity-related complications in mice., Abstract: Obesity is associated with systemic insulin resistance and numerous metabolic disorders. Yet, the mechanisms underlying impaired insulin action during obesity remain to be fully elucidated. Afadin is a multifunctional scaffold protein with the ability to modulate insulin action through its phosphorylation at S1795 in adipocytes. In the present study, we report that insulin-stimulated Afadin S1795 phosphorylation is not restricted to adipose tissues, but is a common signalling event in insulin-responsive tissues including muscle, liver, pancreas and heart. Furthermore, a dynamic regulation of Afadin abundance occurred during diet-induced obesity progression, while its phosphorylation was progressively attenuated. To investigate the role of Afadin S1795 phosphorylation in the regulation of whole-body metabolic homeostasis, we generated a phospho-defective mouse model (Afadin SA) in which the Afadin phosphorylation site was silenced (S1795A) at the whole-body level using CRISPR-Cas9-mediated gene editing. Metabolic characterization of these mice under basal physiological conditions or during a high-fat diet (HFD) challenge revealed that preventing Afadin S1795 phosphorylation improved insulin sensitivity and glucose tolerance and increased liver glycogen storage in the early stage of diet-induced metabolic dysregulation, without affecting body weight. Together, our findings reveal that Afadin S1795 phosphorylation in metabolic tissues is critical during obesity progression and contributes to promote systemic insulin resistance and glucose intolerance in the early phase of diet-induced obesity., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Pancreatic duct cells are equipped with acid/base transporters important for exocrine secretion. Pancreatic ductal adenocarcinoma (PDAC) cells may utilize such transporters to acidify extracellular tumor microenvironment, creating a niche favoring cell proliferation, fibrosis and resistance to chemotherapy-all contributing to the notoriously bad prognosis of this disease. Here, we report that gastric and non-gastric H + , K + -ATPases (coded by ATP4A and ATP12A ) are overexpressed in human and murine pancreatic cancer and that we can target them specifically with proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) in in vitro models of PDAC. Focusing on pantoprazole, we show that it significantly reduced human cancer cell proliferation by inhibiting cellular H + extrusion, increasing K + conductance and promoting cyclin D1-dependent cell cycle arrest and preventing STAT3 activation. Pantoprazole also decreased collagen secretion from pancreatic stellate cells. Importantly, in vivo studies show that pantoprazole treatment of tumor-bearing mice reduced tumor size, fibrosis and expression of angiogenic markers. This work provides the first evidence that H + , K + -ATPases contribute to PDAC progression and that these can be targeted by inhibitors of these pumps, thus proving a promising therapeutic strategy.

Insulin orchestrates metabolic homeostasis through a complex signaling network for which the precise mechanisms controlling its fine-tuning are not completely understood. Here, we report that Afadin, a scaffold protein, is phosphorylated on S1795 (S1718 in humans) in response to insulin in adipocytes, and this phosphorylation is impaired with obesity and insulin resistance. In turn, loss of Afadin enhances the response to insulin in adipose tissues via upregulation of the insulin receptor protein levels. This happens in a cell-autonomous and phosphorylation-dependent manner. Insulin-stimulated Afadin-S1795 phosphorylation modulates Afadin binding with interaction partners in adipocytes, among which HDAC6 preferentially interacts with phosphorylated Afadin and acts as a key intermediate to suppress insulin receptor protein levels. Adipose tissue-specific Afadin depletion protects against insulin resistance and improves glucose homeostasis in diet-induced obese mice, independently of adiposity. Altogether, we uncover a novel insulin-induced cellular feedback mechanism governed by the interaction of Afadin with HDAC6 to negatively control insulin action in adipocytes, which may offer new strategies to alleviate insulin resistance., (© 2019 The Authors.)