Safety of Extending Implanted Vascular Access Device Maintenance Flush Frequency.

Background: Standards of care and guidelines acknowledge insufficient evidence that defines frequency of flushing for implanted vascular access devices (IVADs). Manufacturers recommend 4 weeks, but guidelines suggest that extending to 12 weeks is safe based on functionality.

Objectives: The study reviewed current standards of care for IVAD flush maintenance frequency, examined the characteristics of blood from IVADs by aspirating and observing contents prior to flushing when maintenance care is delayed beyond four weeks, and identified whether more research is required to determine optimal IVAD maintenance flush frequency.

Differential sensitivity of human islets from obese versus lean donors to chronic high glucose or palmitate.

Background: Due to the shortage of multi-organ donors, human pancreatic islet transplantation has now been extended to islets originating from obese subjects. In this study, our aim is to compare the respective sensitivity of human islets from lean vs obese donors to chronic high glucose or high palmitate.

Methods: Human islets were isolated from pancreases harvested from brain-dead multi-organ donors.

Possible protective effect of membrane lipid rafts against interleukin-1β-mediated anti-proliferative effect in INS-1 cells.

We recently reported that pancreatic islets from pre-diabetic rats undergo an inflammatory process in which IL-1β takes part and controls β-cell function. In the present study, using the INS-1 rat pancreatic β-cell line, we investigated the potential involvement of membrane-associated cholesterol-enriched lipid rafts in IL-1β signaling and biological effects on insulin secretion, β-cell proliferation and apoptosis. We show that, INS-1 cells exposure to increasing concentrations of IL-1β leads to a progressive inhibition of insulin release, an increase in the number of apoptotic cells and a dose-dependent decrease in pancreatic β-cell proliferation.

Counteracting neuronal nitric oxide synthase proteasomal degradation improves glucose transport in insulin-resistant skeletal muscle from Zucker fa/fa rats.

Aims/hypothesis: Insulin-mediated glucose transport and utilisation are decreased in skeletal muscle from type 2 diabetic and glucose-intolerant individuals because of alterations in insulin receptor signalling, GLUT4 translocation to the plasma membrane and microvascular blood flow. Catalytic activity of the muscle-specific isoform of neuronal nitric oxide synthase (nNOS) also participates in the regulation of glucose transport and appears to be decreased in a relevant animal model of drastic insulin resistance, the obese Zucker fa/fa rat. Our objective was to determine the molecular mechanisms involved in this defect.

Obesity, insulin resistance and diabetes in the sand rat exposed to a hypercaloric diet; possible protective effect for IL1-β.

It is well established that, upon changing their natural desert low caloric (succulent halophilic plants) to a regular laboratory high caloric diet, sand rats undergo various phenotypic changes depending on their genetic background and including obesity and various degrees of insulin resistance. Our aim was to investigate the acute effects of Interleukin-1β (IL-1β) and Interferon-γ (IFN-γ) on glucose-induced insulin secretion in normal lean sand rats maintained on their natural diet and in obese insulin resistant normoglycemic or type 2 diabetic animals after a 9-month high caloric diet. Animals were fed either a low or a high caloric diet; after 9 months, pancreatic islets were isolated and incubated in the presence of increasing cytokine concentrations.

M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells.

Excessive food intake, obesity and inflammation process in Zucker fa/fa rat pancreatic islets.

Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction.

Is static magnetic field exposure a new model of metabolic alteration? Comparison with Zucker rats.

Purpose: The aim of this study was to investigate if the metabolic alterations observed after static magnetic field (SMF) exposure participates in the development of a pre-diabetic state. A comparison study using the insulin resistant animal model, the Zucker rat and the SMF-exposed Wistar rat was carried out.

Materials And Methods: Zucker rats were compared to Wistar rats either exposed to a 128 mT or 0 mT SMF (sham exposed) and analysed.

Absence of anti-pendrin auto-antibodies in the sera of Tunisian patients with autoimmune thyroid diseases.

Background: We previously demonstrated that the PDS gene is involved in the genetic susceptibility to autoimmune thyroid diseases (AITD) in Tunisia. In the same population, we now investigated the presence of anti-pendrin auto-antibodies (aAbs) in AITD patients' sera.

Methods: Thirty seven Tunisian AITD patients and 19 healthy subjects from families previously linked to the PDS gene, 75 unrelated patients and 20 healthy unrelated subjects were included in our study.

Effects of exposure to a 128-mT static magnetic field on glucose and lipid metabolism in serum and skeletal muscle of rats.

Background And Aims: Increasing environmental pollution may participate in the growing incidence of metabolic disorders. Static magnetic fields (SMFs) are an emerging environmental health issue due to increased exposure in residential and commercial areas; however, their metabolic effects in serum and skeletal muscle are largely unknown. The aim of this study was to investigate the effect of SMF exposure on glucose and lipid metabolism in serum and skeletal muscles of rats.

Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide.

Background: Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis.

Methodology: We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats).

P2 purinergic signalling in the pancreatic beta-cell: control of insulin secretion and pharmacology.

Extracellular adenosine triphosphate is able to modulate pancreatic beta-cell function, acting on P2 purinergic ionotropic (P2X) and metabotropic (P2Y) receptors. Physiologically, ATP entrains beta-cells into a common rhythm by coordinating Ca(2+) oscillations; it plays a central role in insulin secretion pulsatility. ATP also triggers a positive feedback signal amplifying glucose-induced insulin release, which argues for a potential pharmacological application.

Expression of purinergic P2Y receptor subtypes by INS-1 insulinoma beta-cells: a molecular and binding characterization.

Purinergic P2Y-receptor agonists amplify glucose-induced insulin secretion from pancreatic beta-cells, thus offering new opportunities for the treatment of type 2 diabetes. However, little is known about which subtypes of purinergic P2Y receptors are expressed in these cells. The INS-1 beta-cell line is used as a model of pancreatic beta-cells, expressing most of their properties.

Protein inhibitor of neuronal nitric oxide synthase (PIN) is a new regulator of glucose-induced insulin secretion.

We previously showed that pancreatic beta-cells express neuronal nitric oxide synthase (nNOS) that controls insulin secretion through two catalytic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now provide evidence that the endogenous protein inhibitor of nNOS (PIN) is expressed in rat pancreatic islets and INS-1 cells. Double-immunofluorescence studies showed a colocalization of PIN with both nNOS and myosin Va in insulin-secreting beta-cells.

P2Y receptor mediated modulation of insulin release by a novel generation of 2-substituted-5'-O-(1-boranotriphosphate)-adenosine analogues.

Purpose: A series of C2-substituted ATP analogues was previously shown to have potent insulin-secreting properties, yet with poor tissue-selectivity for the pancreatic beta-cell. The present study was designed to evaluate the binding profile on beta-cell membranes and the effects on insulin release and pancreatic vascular resistance of a second generation of P2Y(1) receptor agonists, based on C2-substitution of the adenosine 5'-O-(1-boranotriphosphate) scaffold.

Materials And Methods: Functional experiments were performed in the rat isolated pancreas model; binding studies with ATP-alpha-[(35)S] were performed in membrane homogenates from the rat insulinoma INS-1 cell line.

PIN-bodies: a new class of antibody-like proteins with CD4 specificity derived from the protein inhibitor of neuronal nitric oxide synthase.

By inserting the CB1 paratope-derived peptide (PDP) from the anti-CD4 13B8.2 antibody binding pocket into each of the three exposed loops of the protein inhibitor of neuronal nitric oxide synthase (PIN), we have combined the anti-CD4 specificity of the selected PDP with the stability, ease of expression/purification, and the known molecular architecture of the phylogenetically well-conserved PIN scaffold protein. Such "PIN-bodies" were able to bind CD4 with a better affinity and specificity than the soluble PDP; additionally, in competitive ELISA experiments, CD4-specific PIN-bodies were more potent inhibitors of the binding of the parental recombinant antibody 13B8.

Effect of epiregulin on pancreatic beta cell growth and insulin secretion.

The aim of this study was to determine whether epiregulin, a novel member of EGF-related growth factor family, was able to affect proliferation and secretory function of rat insulinoma INS-1E and RINm5F cell lines. A 24 h treatment with epiregulin resulted in a stimulation of INS-1E and RINm5F cells proliferation; this effect was completely blocked in the presence of an anti-epiregulin antibody which did not affect basal DNA synthesis in the absence of added ligand. In acute experiments, epiregulin was able to potentiate insulin release in the presence of glucose or arginine, in the two cell lines.

Pharmacological interventions that directly stimulate or modulate insulin secretion from pancreatic beta-cell: implications for the treatment of type 2 diabetes.

Blood glucose concentration is controlled by a number of hormone and neurotransmitter signals, either increasing or reducing glucose levels in the case of hypoglycemia or hyperglycemia, respectively. The pancreatic beta-cell responds to an increase in circulating glucose levels by a cascade of metabolic and electrophysiological events leading to the secretion of insulin. Type 2 diabetes is a metabolic disorder characterized by chronic hyperglycemia; the progressive pancreatic beta-cell dysfunction, with altered insulin production and secretion, is a major pathophysiological determinant of the disease together with the resistance of insulin-sensitive tissues to the action of the hormone.

Miniglucagon (MG)-generating endopeptidase, which processes glucagon into MG, is composed of N-arginine dibasic convertase and aminopeptidase B.

Miniglucagon (MG), the C-terminal glucagon fragment, processed from glucagon by the MG-generating endopeptidase (MGE) at the Arg17-Arg18 dibasic site, displays biological effects opposite to that of the mother-hormone. This secondary processing occurs in the glucagon- and MG-producing alpha-cells of the islets of Langerhans and from circulating glucagon. We first characterized the enzymatic activities of MGE in culture media from glucagon and MG-secreting alphaTC1.

Cellulose membrane supported peptide arrays for deciphering protein-protein interaction sites: the case of PIN, a protein with multiple natural partners.

Cellulose membrane supported peptide arrays, prepared according to the Spot method, allow the rapid identification and characterization of protein-protein interaction sites. Here, the method was used to screen reactive peptides from different proteins that bind to a single molecule, the PIN protein. PIN possesses two binding grooves, that have been shown to interact with several targets, including neuronal NO synthase, dynein intermediate chain, myosin V, the proapoptotic protein Bim, the scaffolding proteins DAP1alpha and gephyrin, and the transcription factor NRF-1.

Changes in the dimeric state of neuronal nitric oxide synthase affect the kinetics of secretagogue-induced insulin response.

We previously showed that pancreatic beta-cells express a neuronal isoform of nitric oxide synthase (nNOS) that controls insulin secretion by exerting two enzymatic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now bring evidence that two inhibitors of nNOS, N-omega-nitro-l-arginine methyl ester (l-NAME) and 7-nitroindazole (7-NI), increase glucose-induced insulin secretion but affect beta-cell function differently. In the presence of l-NAME, insulin response is monophasic, whereas 7-NI preserves the normal biphasic secretory pattern.

Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat.

ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different rat models of insulin resistance, i.

Cellular distribution and contribution of cyclooxygenase COX-2 to diabetogenesis in NOD mouse.

Unlike most other mammalian cells, beta-cells of Langerhans constitutively express cyclooxygenase (COX)-2 rather than COX-1. COX-2 is also constitutively expressed in type 1 diabetes (T1D) patients' periphery blood monocytes and macrophage. To understand the role of COX-2 in the beta-cell, we investigated COX-2 expression in beta-cells and islet infiltrates of NOD and BALB/c mice using fluorescence immunohistochemistry and cytochemical confocal microscopy and Western blotting.

Miniglucagon (glucagon 19-29): a novel regulator of the pancreatic islet physiology.

Miniglucagon, the COOH-terminal (19-29) fragment processed from glucagon, is a potent and efficient inhibitor of insulin secretion from the MIN 6 beta-cell line. Using the rat isolated-perfused pancreas, we investigated the inhibitory effect of miniglucagon on insulin secretion and evaluated the existence of an inhibitory tone exerted by this peptide inside the islet. Miniglucagon dose-dependently inhibited insulin secretion stimulated by 8.