Beta-Cell-Specific Expression of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 5 Aggravates High-Fat Diet-Induced Impairment of Islet Insulin Secretion in Mice.

Nicotinamide adenine dinucleotide phosphate oxidases (NOX-es) produce reactive oxygen species and modulate β-cell insulin secretion. Islets of type 2 diabetic subjects present elevated expression of NOX5. Here, we sought to characterize regulation of NOX5 expression in human islets and to uncover the relevance of NOX5 in islet function using a novel mouse model expressing NOX5 in doxycycline-inducible, β-cell-specific manner (RIP/rtTA/NOX5 mice).

Gastrointestinal Hormones Manipulation to Counteract Metabolic Syndrome Using Duodenal Targeted Embolization.

Purpose: Targeted embolization of gastrointestinal (GI) arteries can modify hormonal production. We aimed to evaluate the impact of the embolization of the gastroduodenal artery (GDA) on the activity of foregut mucosa.

Methods: The GDA's duodenal branch was embolized in 12 Yucatan pigs using 100-300 µm (group A; n = 4) or 300-500 µm (group B; n = 4) microspheres, followed by coiling of the branch.

Treatment of NASH with Antioxidant Therapy: Beneficial Effect of Red Cabbage on Type 2 Diabetic Rats.

Aims: Oxidative stress (OS) plays a major role in type 2 diabetes and its vascular and hepatic complications, and novel therapeutic approaches include natural antioxidants. Our previous chemical and biological studies demonstrated the antioxidant activities of red cabbage (RC), and here, we aimed to determine the effects of 2-month long RC consumption using a high-fat/high-fructose model of diabetic rats.

Results: This vegetable, associated with lifestyle measurement, was shown to decrease OS and increase vascular endothelial NO synthase expression, ensuring vascular homeostasis.

Beneficial effects of cherry consumption as a dietary intervention for metabolic, hepatic and vascular complications in type 2 diabetic rats.

Background: Oxidative stress (OS) plays an important role in type 2 diabetes (T2D) pathogenesis and its complications. New therapies target natural antioxidants as an alternative and/or supplemental strategy to prevent and control them. Our previous chemical and biological studies highlighted the important antioxidant activities of cherries, among other fruits and vegetables, thus we aimed to determine in vivo effects of 2-month long cherry consumption using a high-fat/high-fructose (HFHF) model of diabetic-rats (Lozano et al.

Oral insulin delivery, the challenge to increase insulin bioavailability: Influence of surface charge in nanoparticle system.

Oral administration of insulin increases patient comfort and could improve glycemic control thanks to the hepatic first passage. However, challenges remain. The current approach uses poly (d, lactic-co-glycolic) acid (PLGA) nanoparticles (NPs), an effective drug carrier system with a long acting profile.

Comparison of Perfluorodecalin and HEMOXCell as Oxygen Carriers for Islet Oxygenation in an In Vitro Model of Encapsulation.

Transplantation of encapsulated islets in a bioartificial pancreas is a promising alternative to free islet cell therapy to avoid immunosuppressive regimens. However, hypoxia, which can induce a rapid loss of islets, is a major limiting factor. The efficiency of oxygen delivery in an in vitro model of bioartificial pancreas involving hypoxia and confined conditions has never been investigated.

A Metabolomic Approach (H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers.

Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation.

Improvement of islet graft function using liraglutide is correlated with its anti-inflammatory properties.

Background And Purpose: Liraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti-inflammatory and anti-oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo.

Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model.

Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues.

In Vitro and In Vivo Investigation of the Angiogenic Effects of Liraglutide during Islet Transplantation.

Introduction: This study investigated the angiogenic properties of liraglutide in vitro and in vivo and the mechanisms involved, with a focus on Hypoxia Inducible Factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR).

Materials And Methods: Rat pancreatic islets were incubated in vitro with 10 μmol/L of liraglutide (Lira) for 12, 24 and 48 h. Islet viability was studied by fluorescein diacetate/propidium iodide staining and their function was assessed by glucose stimulation.

High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications.

Background: As a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is particularly used in prepared foods and carbonated beverages. We investigated the impact of regular consumption of fructose, in combination or not with fatty food, on the onset of metabolic syndrome and type 2 diabetes (T2D).

Beneficial effects of a red wine polyphenol extract on high-fat diet-induced metabolic syndrome in rats.

Purpose: Individuals with metabolic syndrome (MS) show several metabolic abnormalities including insulin resistance, dyslipidaemia, and oxidative stress (OS). Diet is one of the factors influencing the development of MS, and current nutritional advice emphasises the benefits of fruit and vegetable consumption. Here, we assessed the effects of naturally occurring antioxidants, red wine polyphenols (RWPs), on MS and OS.

Impact of Pancreatic Rat Islet Density on Cell Survival during Hypoxia.

In bioartificial pancreases (BP), the number of islets needed to restore normoglycaemia in the diabetic patient is critical. However, the confinement of a high quantity of islets in a limited space may impact islet survival, particularly in regard to the low oxygen partial pressure (PO2) in such environments. The aim of the present study was to evaluate the impact of islet number in a confined space under hypoxia on cell survival.

Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells.

The in vitro methods currently used to screen bioactive compounds focus on the use of a single model of oxidative stress. However, this simplistic view may lead to conflicting results. The aim of this study was to evaluate the antioxidant properties of two natural extracts (a mix of red wine polyphenols (RWPs) and epigallocatechin gallate (EGCG)) with three models of oxidative stress induced with hydrogen peroxide (H2O2), a mixture of hypoxanthine and xanthine oxidase (HX/XO), or streptozotocin (STZ) in RINm5F beta cells.

Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy.

Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg).

Portal or subcutaneous insulin infusion: efficacy and impact on liver inflammation.

Intraperitoneal insulin allows physiological portal insulin administration and first-pass hepatic insulin extraction, but the impact on liver metabolism and inflammation is unknown. Our objective was to compare the impact, on metabolic control and liver function, of the same dose of insulin administered either intraperitoneally or subcutaneously during continuous infusion in diabetic rats. Wistar rats were randomly divided into 4 groups: control (C), untreated diabetic (streptozotocin, 100 mg/kg) and diabetic rats treated by continual subcutaneous Insuplant® infusion (CSII) and continual intraperitoneal Insuplant(®) infusion (CPII) of 2 UI/200 g/day (via an osmotic mini-pump for 1-4 weeks).

Design, characterisation, and bioefficiency of insulin-chitosan nanoparticles after stabilisation by freeze-drying or cross-linking.

Insulin delivery by oral route would be ideal, but has no effect, due to the harsh conditions of the gastrointestinal tract. Protection of insulin using encapsulation in self-assembled particles is a promising approach. However, the lack of stability of this kind of particles in biological environments induces a low bioavailability of encapsulated insulin after oral administration.

Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome.

Disruption of the pancreatic islet environment combined with the decrease in oxygen supply that occurs during isolation leads to poor islet survival. The aim of this study was to validate the benefit of using a plasma-based scaffold supplemented with perfluorodecalin to improve islet transplantation outcome. Rat islets were cultured in three conditions: i) control group, ii) plasma based-matrix (P-matrix), and iii) P-matrix supplemented with emulsified perfluorodecalin.

Pro-inflammatory and pro-oxidant status of pancreatic islet in vitro is controlled by TLR-4 and HO-1 pathways.

Since their isolation until implantation, pancreatic islets suffer a major stress leading to the activation of inflammatory reactions. The maintenance of controlled inflammation is essential to preserve survival and function of the graft. Identification and targeting of pathway(s) implicated in post-transplant detrimental inflammatory events, is mandatory to improve islet transplantation success.

Metabolic and oxidative stress markers in Wistar rats after 2 months on a high-fat diet.

Background: Metabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress.

Role of islet culture on angiogenic and inflammatory mechanisms.

Early events hampering islet engraftment may relate to instant blood-mediated inflammatory reaction (IBMIR) and to insufficient islet revascularization inducing β-cell death. We evaluated the influence of time of culture on angiogenic and inflammatory cellular mechanisms in islet loss in vitro. Rat pancreatic islets cultured for 0, 12, 24, and 48 hours were assessed for functionality using glucose stimulation tests and identification of signaling pathways using polymerase chain reaction (PCR) arrays.

Instant blood-mediated inflammatory reaction during islet transplantation: the role of Toll-like receptors signaling pathways.

The instant blood-mediated inflammatory reaction (IBMIR) leads to massive destruction of transplanted islets. Islet isolation and time of culture may elicit the release of potent activators of Toll-like receptors (TLRs) signaling pathways during IBMIR. This work sought to evaluate the role of TLR signaling pathways to mediate inflammatory reactions.

Duodenum-specific drug delivery: in vivo assessment of a pharmaceutically developed enteric-coated capsule for a broad applicability in rat studies.

Targeting new oral drug formulations in the intestine has a broad applicability in animal studies. Enteric-coated capsules are gastroresistant and specific drug delivery systems useful for the evaluation of new pharmaceutical formulations during pre-clinical validations in rats. The purpose of this study was to develop and validate in a large-scale, reliable, reproducible capsules, to offer a safe and standardized duodenum-specific delivery system adapted for studies in rats.

Perfluorocarbon emulsions prevent hypoxia of pancreatic β-cells.

As oxygen carriers, perfluorocarbon emulsions might be useful to decrease hypoxia of pancreatic islets before transplantation. However, their hydrophobicity prevents their homogenisation in culture medium. To increase the surface of contact between islets and Perfluorooctyl bromide (PFOB), and consequently oxygen delivery, we tested effect of a PFOB emulsion in culture medium on β-cell lines and rat pancreatic islets.

Improvement of rat islet viability during transplantation: validation of pharmacological approach to induce VEGF overexpression.

Delayed and insufficient revascularization during islet transplantation deprives islets of oxygen and nutrients, resulting in graft failure. Vascular endothelial growth factor (VEGF) could play a critical role in islet revascularization. We aimed to develop pharmacological strategies for VEGF overexpression in pancreatic islets using the iron chelator deferoxamine (DFO), thus avoiding obstacles or safety risks associated with gene therapy.