BMAL1 modulates ROS generation and insulin secretion in pancreatic β-cells: An effect possibly mediated via NOX2.

The pancreatic β cells circadian clock plays a relevant role in glucose metabolism. NADPH oxidase (NOX) family is responsible for producing reactive oxygen species (ROS), such as superoxide anion and hydrogen peroxide, using NADPH as an electron donor. In pancreatic β-cells, NOX-derived ROS inhibits basal and glucose-stimulated insulin secretion.

Metformin disrupts insulin secretion, causes proapoptotic and oxidative effects in rat pancreatic beta-cells in vitro.

Metformin is the first-line drug to treat type 2 diabetes mellitus. Its mechanism of action is still debatable, and recent studies report that metformin attenuates oxidative stress. This study evaluated the in vitro antioxidant effects of a broad range of metformin concentrations on insulin-producing cells.

Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress.

A high caloric intake, rich in saturated fats, greatly contributes to the development of obesity, which is the leading risk factor for type 2 diabetes (T2D). A persistent caloric surplus increases plasma levels of fatty acids (FAs), especially saturated ones, which were shown to negatively impact pancreatic β-cell function and survival in a process called lipotoxicity. Lipotoxicity in β-cells activates different stress pathways, culminating in β-cells dysfunction and death.

Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts β-Cell Function and Survival.

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 the events triggered and the role of different ROS sources remain unclear. Isolated islets from C57BL/6J wild-type (WT), NOX1 KO and NOX2 KO mice were exposed to a PIC combination.

Melatonin regulates maternal pancreatic remodeling and B-cell function during pregnancy and lactation.

The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well-known the role of melatonin in the maintenance of the endocrine pancreas and its tropism. Studies indicate increasing nocturnal serum concentrations of maternal melatonin during pregnancy in both humans and rodents.

Transient NADPH oxidase 2-dependent HO production drives early palmitate-induced lipotoxicity in pancreatic islets.

Modern lifestyles, including lack of physical activity and poor nutritional habits, are driving the rapidly increasing prevalence of obesity and type 2 diabetes. Increased levels of free fatty acids (FFAs), particularly saturated FFAs, in obese individuals have been linked to pancreatic β-cell failure. This process, termed lipotoxicity, involves activation of several stress responses, including ER stress and oxidative stress.

Effects of lixisenatide treatment on mild cachexia and related metabolic abnormalities in Walker-256 tumour-bearing rats.

Lixisenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used in the treatment of type 2 diabetes mellitus (T2DM). It increases insulin (INS) secretion and can decrease INS resistance, improving metabolic disorders in this disease. However, its effects on metabolic disturbances in cancer-bearing, which also exhibit decreased INS secretion and INS resistance, changes that may contribute to weight loss (cachexia), have not yet been evaluated.

Evidence for NADPH oxidase activation by GPR40 in pancreatic β-cells.

Investigate the involvement of the fatty acids receptor GPR40 in the assembly and activation of NADPH oxidase and the implications on pancreatic β-cell function. BRIN-BD11 β-cells were exposed to GPR40 agonist (GW9508) or linoleic acid in different glucose concentrations. Superoxide and HO were analyzed, respectively, by DHE fluorescence and by fluorescence of the HO sensor, roGFP2-Orp1.

Intermittent Fasting for Twelve Weeks Leads to Increases in Fat Mass and Hyperinsulinemia in Young Female Wistar Rats.

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

Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic β-cell physiology and function.

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 insulin secretion. On the contrary, long-term exposure to saturated FFAs results in decreased insulin secretion, as well as triggering oxidative stress and endoplasmic reticulum (ER) stress, culminating in cell death.

The insulin resistance is reversed by exogenous 3,5,3'triiodothyronine in type 2 diabetic Goto-Kakizaki rats by an inflammatory-independent pathway.

Purpose: Diabetes mellitus (DM) has a multifactorial etiology that imparts a particular challenge to effective pharmacotherapy. Thyroid hormone actions have demonstrated beneficial effects in diabetic as well as obese rats. In both conditions, inflammation status plays a crucial role in the development of insulin resistance.

Short-term high glucose culture potentiates pancreatic beta cell function.

The exposure of pancreatic islets to high glucose is believed to be one of the causal factors of the progressive lowering of insulin secretion in the development of type 2 diabetes. The progression of beta cell failure to type 2 diabetes is preceded by an early positive increase in the insulin secretory response to glucose, which is only later followed by a loss in the secretion capacity of pancreatic islets. Here we have investigated the electrophysiological mechanisms underlying the early glucose-mediated gain of function.

Chronic treatment with dexamethasone alters clock gene expression and melatonin synthesis in rat pineal gland at night.

Background: Melatonin is a neuroendocrine hormone that regulates many functions involving energy metabolism and behavior in mammals throughout the light/dark cycle. It is considered an output signal of the central circadian clock, located in the suprachiasmatic nucleus of the hypothalamus. Melatonin synthesis can be influenced by other hormones, such as insulin and glucocorticoids in pathological conditions or during stress.

Effects of metformin on insulin resistance and metabolic disorders in tumor-bearing rats with advanced cachexia.

Metformin (MET) is widely used in the correction of insulin (INS) resistance and metabolic abnormalities in type 2 diabetes. However, its effect on INS resistance and metabolic disorders associated with cancer cachexia is not established. We investigated the MET effects, isolated or associated with INS, on INS resistance and metabolic changes induced by Walker-256 tumor in rats with advanced cachexia.

Zinc Supplementation Improves Glucose Homeostasis in High Fat-Fed Mice by Enhancing Pancreatic β-Cell Function.

Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and β-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl₂ (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl₂ (HFZ).

Insulin, not glutamine dipeptide, reduces lipases expression and prevents fat wasting and weight loss in Walker 256 tumor-bearing rats.

Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.

Pioglitazone improves insulin sensitivity and reduces weight loss in Walker-256 tumor-bearing rats.

Aim: The lipogenic effect of pioglitazone (PGZ), an insulin (INS) sensitizer, is well established. However, few studies have evaluated PGZ effects in preventing weight loss in cancer. We investigated PGZ effects, alone or associated with INS, on INS resistance, cachexia and metabolic abnormalities induced by Walker-256 tumor in rats.

Melatonin modifies basal and stimulated insulin secretion via NADPH oxidase.

Melatonin is a hormone synthesized in the pineal gland, which modulates several functions within the organism, including the synchronization of glucose metabolism and glucose-stimulated insulin secretion (GSIS). Melatonin can mediate different signaling pathways in pancreatic islets through two membrane receptors and via antioxidant or pro-oxidant enzymes modulation. NADPH oxidase (NOX) is a pro-oxidant enzyme responsible for the production of the reactive oxygen specie (ROS) superoxide, generated from molecular oxygen.

L-Arginine supplementation improves insulin sensitivity and beta cell function in the offspring of diabetic rats through AKT and PDX-1 activation.

Maternal hyperglycemia can result in defects in glucose metabolism and pancreatic β-cell function in offspring. The purpose of this study was to evaluate the impact of maternal diabetes mellitus on pancreatic islets, muscle and adipose tissue of the offspring, with or without oral l-Arginine supplementation. The induction of diabetes was performed using streptozotocin (60mg/kg).

NADPH oxidase-2 does not contribute to β-cell glucotoxicity in cultured pancreatic islets from C57BL/6J mice.

High glucose-induced oxidative stress and increased NADPH oxidase-2 (NOX2) activity may contribute to the progressive decline of the functional β-cell mass in type 2 diabetes. To test that hypothesis, we characterized, in islets from male NOX2 knockout (NOX2-KO) and wild-type (WT) C57BL/6J mice cultured for up to 3 weeks at 10 or 30 mmol/l glucose (G10 or G30), the in vitro effects of glucose on cytosolic oxidative stress using probes sensing glutathione oxidation (GRX1-roGFP2), thiol oxidation (roGFP1) or HO (roGFP2-Orp1), on β-cell stimulus-secretion coupling events and on β-cell apoptosis. After 1-2 days of culture in G10, the glucose stimulation of insulin secretion (GSIS) was ∼1.

Control of Insulin Secretion by Production of Reactive Oxygen Species: Study Performed in Pancreatic Islets from Fed and 48-Hour Fasted Wistar Rats.

Mitochondria and NADPH oxidase are important sources of reactive oxygen species in particular the superoxide radical (ROS) in pancreatic islets. These molecules derived from molecular oxygen are involved in pancreatic β-cells signaling and control of insulin secretion. We examined the involvement of ROS produced through NADPH oxidase in the leucine- and/or glucose-induced insulin secretion by pancreatic islets from fed or 48-hour fasted rats.

Colonic Fermentation of Unavailable Carbohydrates from Unripe Banana and its Influence over Glycemic Control.

The aim of this study was to evaluate the effect of the colonic fermentation of unavailable carbohydrates from unripe banana (mass - UBM - and starch - UBS) over parameters related to glucose and insulin response in rats. Wistar male rats were fed either a control diet, a UBM diet (5 % resistant starch - RS) or a UBS diet (10 % RS) for 28 days. In vivo (oral glucose tolerance test) and in vitro (cecum fecal fermentation, pancreatic islet insulin secretion) analyses were performed.

Omega-3 supplementation improves pancreatic islet redox status: in vivo and in vitro studies.

Objectives: The aim of the study was to evaluate the potential changes induced by fish oil (FO) supplementation on the redox status of pancreatic islets from healthy rats. To test whether these effects were due to eicosapentaenoic acid and docosahexaenoic acid (ω-3), in vitro experiments were performed.

Methods: Rats were supplemented with FO, and pancreatic islets were obtained.

DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet.

Dehydroepiandrosterone (DHEA) and the dehydroepiandrosterone sulfate (DHEA-S) are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX) female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS) and pancreatic islet function.

Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulation.

Excess of glucocorticoids (GCs) during pregnancy is strongly associated with the programming of glucose intolerance in the offspring. However, the impact of high GC levels on maternal metabolism is not clearly documented. This study aimed to test the hypothesis that mothers exposed to elevated levels of GCs might also display long-term disturbances in glucose homeostasis.