Glucagon-like peptide 1 receptor activation: anti-inflammatory effects in the brain.

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity. Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues, including different brain regions. Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection, like the support of cell growth/survival, enhancement promotion of synapse formation, autophagy, and inhibition of the secretion of proinflammatory cytokines, microglial activation, and apoptosis during neural morphogenesis.

Anti-Inflammatory Effects of GLP-1 Receptor Activation in the Brain in Neurodegenerative Diseases.

The glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone well known for its incretin effect in the glucose-dependent stimulation of insulin secretion. However, GLP-1 is also produced in the brain and displays a critical role in neuroprotection and inflammation by activating the GLP-1 receptor signaling pathways. Several studies in vivo and in vitro using preclinical models of neurodegenerative diseases show that GLP-1R activation has anti-inflammatory properties.

Renin-Angiotensin System in Liver Metabolism: Gender Differences and Role of Incretins.

The impaired hepatic lipids and carbohydrates metabolism result in various metabolic disorders, including obesity, diabetes, insulin resistance, hyperlipidemia and metabolic syndrome. The renin-angiotensin system (RAS) has been identified in the liver and it is now recognized as an important modulator of body metabolic processes. This review is intended to provide an update of the impact of the renin-angiotensin system on lipid and carbohydrate metabolism, regarding gender difference and prenatal undernutrition, specifically focused on the role of the liver.

Effects of Glucagon-like peptide 1 (GLP-1) analogs in the hippocampus.

The glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone very well known for its incretin effect in the glucose-dependent stimulation of insulin secretion. However, GLP-1 is also produced in the brain, and it displays critical roles in neuroprotection by activating the GLP-1 receptor signaling pathways. GLP-1 enhances learning and memory in the hippocampus, promotes neurogenesis, decreases inflammation and apoptosis, modulates reward behavior, and reduces food intake.

Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress.

Glucagon like-peptide 1 (GLP-1) within the brain is produced by a population of preproglucagon neurons located in the caudal nucleus of the solitary tract. These neurons project to the hypothalamus and another forebrain, hindbrain, and mesolimbic brain areas control the autonomic function, feeding, and the motivation to feed or regulate the stress response and the hypothalamic-pituitary-adrenal axis. GLP-1 receptor (GLP-1R) controls both food intake and feeding behavior (hunger-driven feeding, the hedonic value of food, and food motivation).

GLP-1 receptor agonist ameliorates experimental lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease. This disease is characterized by an excessive accumulation of extracellular matrix deposition that modify normal lung physiology. Up to date, there are not efficient therapeutic tools to fight IPF.

Perinatal Undernutrition, Metabolic Hormones, and Lung Development.

Maternal and perinatal undernutrition affects the lung development of litters and it may produce long-lasting alterations in respiratory health. This can be demonstrated using animal models and epidemiological studies. During pregnancy, maternal diet controls lung development by direct and indirect mechanisms.

Stressing diabetes? The hidden links between insulinotropic peptides and the HPA axis.

Diabetes mellitus exerts metabolic stress on cells and it provokes a chronic increase in the long-term activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, perhaps thereby contributing to insulin resistance. GLP-1 receptor (GLP-1R) agonists are pleiotropic hormones that not only affect glycaemic and metabolic control, but they also produce many other effects including activation of the HPA axis. In fact, several of the most relevant effects of GLP-1 might involve, at least in part, the modulation of the HPA axis.

GLP-1 Increases Preovulatory LH Source and the Number of Mature Follicles, As Well As Synchronizing the Onset of Puberty in Female Rats.

Control of estrous cycle and reproductive capacity involves a large number of central and peripheral factors, integrating numerous nutritional and metabolic signals. Here we show that glucagon-like peptide-1 (GLP-1), a peptide with anorexigenic and insulinotropic actions, and the GLP-1 receptor agonist Exendin-4 (Ex4) exert a regulatory influence on the gonadal axis, in both adult and prepubertal female rats. In adult rats, Glp-1 receptor expression varies during the estrous cycle at the hypothalamus, pituitary, and ovary.

Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats.

Diabetes alters microvascular function in the vascular beds of organs, including the lungs. Cardiovascular complications of pulmonary vascular affectation may be a consequence of the overactivation of the vasoconstrictive and proliferative components of the renin-angiotensin system. We previously reported that pulmonary physiology and surfactant production is improved by the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide (LIR) in a rat model of lung hypoplasia.

Corticotropin-releasing hormone and the sympathoadrenal system are major mediators in the effects of peripherally administered exendin-4 on the hypothalamic-pituitary-adrenal axis of male rats.

Glucagon-like peptide-1 (GLP-1) and the GLP-1 receptor agonist, exendin-4 (Ex-4), potently stimulate hypothalamic-pituitary-adrenal (HPA) axis activity after either central or peripheral administration. Because several GLP-1 derivative drugs, including synthetic Ex-4, are currently in use to treat patients with type II diabetes mellitus, the characterization of Ex-4 effects on the HPA axis is highly relevant. Herein, the roles of CRH and AVP on these effects were investigated by administering the antagonists astressin and d(CH2)5Tyr(Me)AVP, respectively.

Effects of prolonged exendin-4 administration on hypothalamic-pituitary-adrenal axis activity and water balance.

Exendin-4 (Ex-4) is a natural agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently being used as a treatment for type 2 diabetes mellitus due to its insulinotropic properties. Previous studies have revealed that acute administration of both GLP-1 and, in particular, Ex-4 potently stimulates hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, the effects of prolonged Ex-4 exposure on HPA function were explored.

Pulmonary GLP-1 receptor increases at birth and exogenous GLP-1 receptor agonists augmented surfactant-protein levels in litters from normal and nitrofen-treated pregnant rats.

The glucagon-like peptide-1 receptor (GLP-1R) is found in a variety of tissues outside of the pancreas. For example, GLP-1R is expressed in the lung, where it has been implicated in the regulation of the lipid fraction of surfactants, suggesting it fulfills an important role in lung function. Here, we show that GLP-1R expression is strongly up-regulated immediately after birth in neonatal rats, particular in male offspring.

GLP-1(7-36)-amide and Exendin-4 stimulate the HPA axis in rodents and humans.

Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic peptide expressed in the gut and brain, which is secreted in response to food intake. The levels of GLP-1 within the brain have been related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and hence, this peptide might mediate some responses to stress. Nevertheless, there is little information regarding the effects of circulating GLP-1 on the neuroendocrine control of HPA activity.

Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system.

Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats.

[Gastrointestinal hormones in food intake control].

The discovery of gut hormones regulating the energy balance has aroused great interest in the scientific community. Some of these hormones modulate appetite and satiety, acting on the hypothalamus or the solitary tract nucleus in the brainstem. In general, the endocrine signals generated in the gut have direct or indirect (through the autonomous nervous system) anorexigenic effects.

Exendin-4 potently decreases ghrelin levels in fasting rats.

Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and fat-reducing properties.