Calcium (Ca2+) is a key regulator in diverse intracellular signaling pathways and has long been implicated metabolic control mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important Ca2+ buffers affecting cytosolic transients. Excessive matrix known to be deleterious due opening the permeability transition pore (mPTP) consequent membrane potential dissipation, leading swelling, rupture, cell death. Moderate within organelle, on other hand,...

Glutamine availability may be reduced in chronic diseases, such as type 2 diabetes mellitus (T2DM)-induced by obesity. Herein, the antioxidant, anti-inflammatory and lipid metabolism effects of oral glutamine supplementation its free dipeptide form were assessed ob/ob mice. Adult male C57BL/6J mice supplemented with L-alanyl-L-glutamine (DIP) or L-glutamine (GLN) drinking water for 40 days, whilst Wild-type lean (WT) control (CTRL) received fresh only. Plasma tissue (skeletal muscle liver)...

Obesity significantly decreases life expectancy and increases the incidence of age-related dysfunctions, including β-cell dysregulation leading to inadequate insulin secretion. Here, we show that diluted plasma from obese human donors acutely impairs integrity secretion relative lean subjects. Similar results were observed with sera rats fed ad libitum, when compared lean, calorically restricted, animals. The damaging effects circulating factors on β-cells occurs in absence nutrient...

Mitochondria shape intracellular Ca

Fasting is known to cause physiological changes in the endocrine pancreas, including decreased insulin secretion and increased reactive oxygen species (ROS) production. However, there no consensus about long-term effects of intermittent fasting (IF), which can involve up 24 hours interspersed with normal feeding days. In present study, we analyzed alternate-day IF for 12 weeks a developing healthy organism. Female 30-day-old Wistar rats were randomly divided into two groups: control, free...

Prevention of obesity through caloric restriction (CR) is well known to protect many tissues but has been poorly studied in kidneys. Here, we determined the effects long-term CR rat kidney mitochondria, which are central players energy metabolism and aging. Surprisingly, found that diet increased mitochondrial reactive oxygen production permeability transition. This suggests kidneys respond differently restricted diets may be more susceptible under CR.

The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return nonpregnant state right after delivery. Furthermore, it is well-known role melatonin in maintenance and its tropism. Studies indicate increasing nocturnal serum concentrations maternal during pregnancy both humans rodents. present study investigated on energy metabolism pancreatic function remodeling early lactation rats. results confirm that absence impairs glucose...

Evaluation of mitochondrial oxygen consumption and ATP production is important to investigate pancreatic islet pathophysiology. Most studies use cell lines due difficulties in measuring primary respiration, which requires specific equipment consumables, expensive poorly reproducible. Our aim was establish a practical method assess metabolic fluxes using standard commercial consumables. Pancreatic islets were isolated from mice/rats, dispersed with trypsin, adhered pre-coated Seahorse or...

Objective: Investigate the involvement of fatty acids receptor GPR40 in assembly and activation NADPH oxidase implications on pancreatic β-cell function.Methods: BRIN-BD11 β-cells were exposed to agonist (GW9508) or linoleic acid different glucose concentrations. Superoxide H2O2 analyzed, respectively, by DHE fluorescence sensor, roGFP2-Orp1. Protein contents p47phox plasma membrane cytosol analyzed western blot. role was evaluated p22phox siRNA pharmacological inhibition with VAS2870. NOX2...

What is the central question of this study? Type 1 diabetes mellitus (T1D) leads to hyperglycaemia owing pancreatic β-cell destruction by immune system. Physical exercise has been shown have potentially beneficial protective roles against cytokine-induced death, but its benefits are yet be proved and should understood better, especially in islet environment. main finding importance? protects loss a well-described animal model for T1D, induced multiple low doses streptozotocin. This seems...

Abstract Mitochondria shape intracellular Ca 2+ signaling through the concerted activity of uptake via mitochondrial calcium uniporter, and efflux from by Na + /Ca exchangers (NCLX). Here, we describe a novel relationship between NCLX, , autophagic activity. Conditions that stimulate autophagy in vivo vitro, such as caloric restriction nutrient deprivation, upregulate NCLX expression hepatic tissue cells. Conversely, knockdown impairs basal starvation-induced autophagy. Similarly, acute...

Background: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual’s health by predisposing several other diseases. About twice as many women men suffer from severe obesity and, in fact, there are stages woman’s life when weight gain adiposity can result greater damage health. For example, triples the chance of woman developing gestational diabetes. Many hormones promote metabolic adaptations pregnancy, including progesterone, whose role female...

Abstract Background Free fatty acids (FFAs) are known for their dual effects on insulin secretion and pancreatic β-cell survival. Short-term exposure to FFAs, such as palmitate, increases secretion. On the contrary, long-term saturated FFAs results in decreased secretion, well triggering oxidative stress endoplasmic reticulum (ER) stress, culminating cell death. The of can be mediated either via intracellular oxidation consequent cellular metabolism or activation membrane receptor GPR40....

In type 1 diabetes (T1D) development, proinflammatory cytokines (PIC) released by immune cells lead to increased reactive oxygen species (ROS) production in β-cells. Nonetheless, the temporality of events triggered and role different ROS sources remain unclear. Isolated islets from C57BL/6J wild-type (WT), NOX1 KO NOX2 mice were exposed a PIC combination. We show that increase O2•− after 2 h WT but not islets. Using transgenic constitutively expressing genetically encoded compartment...

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)

Metformin is the first-line drug to treat type 2 diabetes mellitus. Its mechanism of action still debatable, and recent studies report that metformin attenuates oxidative stress. This study evaluated in vitro antioxidant effects a broad range concentrations on insulin-producing cells. The cell cycle, metabolism, glucose-stimulated insulin secretion, death were determine biguanide beta-cell function survival. Antioxidant potential was based reactive oxygen species (ROS), reduced glutathione...

Abstract Calcium (Ca 2+ ) is a key regulator in diverse intracellular signaling pathways, and has long been implicated metabolic control mitochondrial function. Mitochondria can actively take up large amounts of Ca , thereby acting as important buffers affecting cytosolic transients. Excessive matrix known to be deleterious due opening the permeability transition pore (mPTP) consequent membrane potential dissipation, leading swelling, rupture, cell death. Moderate within organelle, on other...

Islet transplantation is a promising treatment strategy for type 1 diabetes mellitus (T1DM) patients. However, oxidative stress-induced graft failure due to an insufficient revascularization major problem of this therapeutic approach. NADPH oxidase (NOX)2 important producer reactive oxygen species (ROS) and several studies have already reported that enzyme plays crucial role in the endocrine function viability β-cells. Therefore, we hypothesized targeting islet NOX2 improves outcome...

Nocturnal melatonin secretion is important for preservation of ß-cell mass and function. Knowing that type 2 diabetes mellitus (T2DM) a chronic metabolic disorder characterized by hyperglycemia caused the elevated resistance peripheral tissues to insulin, reduction in pineal disturbances insulin pancreatic ß-cells. In this context, exercise considered one most valuable non-pharmacological approaches treatment T2DM. Considering beneficial role on glycemic metabolism physical exercise, we...

Abstract Aims/hypothesis Efficient mitochondrial oxidative phosphorylation is essential for pancreatic beta cell responses to nutrient levels. Consequently, the evaluation of oxygen consumption and ATP production important investigate aspects islet pathophysiology. Currently, most studies use lines instead primary islets due difficulties in measuring respiration, which requires specific equipment consumables that are expensive, complicated use, poorly reproducible. The aim this study...