oxytocin and Hyperglycemia

The present study aimed to explore the role of oxytocin (OT) in myocardial injury induced by ischemia/reperfusion (I/R) and hyperglycemia and its underlying mechanisms. In this study, the isolated rat hearts underwent I/R in Langendorff perfusion model and H9c2 cells were subjected to hypoxia/reoxygenation (H/R) to establish an in vitro model. I/R injury was induced by exposing the rat hearts to 40 min of global ischemia followed by 60 min of reperfusion. H9c2 cells were cultured under the normoglycemic or hyperglycemic condition with or without pretreatment of OT, and then exposed to 4 h of hypoxia and 2 h of reoxygenation. Measurement indicators included myocardial infarct size assessed by triphenyltetrazolium chloride (TTC) staining and hemodynamic parameters in the ex vivo model as well as cell viability detected by cell counting kit 8 (CCK-8), apoptotic rate evaluated by flow cytometry, and the protein expressions by Western blot. The findings demonstrated that OT attenuated myocardial I/R injury. First, OT preconditioning significantly reduced hemodynamic disorders and myocardial infarct sizes. In addition, OT increased cell viability, decreased cell apoptosis and the expressions of IL-18, IL-1β, cleaved-caspase-1, NLRP3, and GSDMD following H/R. NLRP3 activator nigericin eliminated the beneficial effects of OT in H9c2 cells. Furthermore, OT also activated AMPK and decreased the expressions of pyroptosis-related proteins. Administration of AMPK inhibitor compound C blunted OT-induced AMPK phosphorylation and elevated the expressions of pyroptosis-related proteins in H9c2 cells subjected to H/R with hyperglycemia. OT alleviates myocardial I/R injury with hyperglycemia by inhibiting pyroptosis via AMPK/NLRP3 signaling pathway.

Topics: AMP-Activated Protein Kinases; Animals; Glucose; Hyperglycemia; Hypoxia; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; NLR Family, Pyrin Domain-Containing 3 Protein; Oxytocin; Pyroptosis; Rats; Reperfusion; Signal Transduction

Vasoactive intestinal peptide (VIP) is a neurotransmitter with anorectic effect that acts in the hypothalamus to regulate food intake. Oxytocin is a neuropeptide produced in the hypothalamus that controls energy homeostasis and has an inhibitory role on food intake. Thus, the present study aims at verifying the role of oxytocin as a mediator of VIP on energy homeostasis. For this purpose, intracerebroventricular microinjection of oxytocin receptor antagonist (vasotocin, OVT) or vehicle (NaCl 0.9%) was carried out in male rats, and after 15 min, VIP or saline was microinjected. After 15 min of the second microinjection, food intake was evaluated or euthanasia was undertaken for blood collection. There was a reduction on food intake after VIP microinjection and the pretreatment with OVT partially reversed this effect. Hyperglycemia was observed after VIP microinjection, and pretreatment with OVT partially blocked this effect. Plasma corticosterone concentration was significantly increased after VIP or OVT. Plasma levels of free fatty acids were decreased by VIP, but not when VIP was microinjected after OVT. Thus, OVT partially reversed VIP-induced hypophagia and changes on plasma metabolic parameters, suggesting a role for oxytocin as a mediator of VIP effects on energy homeostasis.

Topics: Animals; Corticosterone; Eating; Energy Metabolism; Hyperglycemia; Male; Oxytocin; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

The goal of this work was to investigate a new nasal carrier for enhanced drug delivery to brain, we call Phospholipid Magnesome. The system contains soft phospholipid vesicles, composed of phospholipid, water, propylene glycol, magnesium salt, and the mucoadhesive polymer, alginate. The carrier was characterized by various methods: electron microscopy, calorimetry, and dynamic light scattering. The ability of the carrier's vesicles to entrap various molecules was studied by CLSM and ultracentrifugation combined with HPLC quantification. Mucoadhesivity of the carrier was tested in vitro using porcine nasal mucosa. The delivery of rohdamine 6G, insulin, and epidermal growth factor was estimated by two methods, multiphoton microscopy and near infrared (NIR) imaging. Pharmacodynamic effects of nasal treatment with oxytocin and insulin incorporated in Phospholipid Magnesome were evaluated in animal models. Results show that the system is composed of soft multilamellar nanosized vesicles with the ability to entrap both lipophilic and hydrophilic molecules. The mucoadhesivity test results indicate a prolonged contact time of the drug with the nasal membrane as compared to control. Multiphoton microscopy and NIR imaging of brain show effective delivery of the tested molecules to brain following nasal administration in Phospholipid Magnesome relative to controls. Moreover, the results of the pharmacodynamic study measuring the antinociceptive effect of oxytocin administrated nasally to an animal model indicate the efficiency of the Phospholipid Magnesome as compared to three control systems. Further, nasal administration of insulin resulted in a strong and prolonged hypoglycemic effect for the drug incorporated in the new carrier but not for control systems. Based on the results of the histopathological test, the carrier is safe for local administration on the nasal membrane. In conclusion, the results of this study suggest that Phospholipid Magnesome nasal carrier is able to improve drug effects, probably by a combined mechanism, absorption enhancement, and prolongation of mucosal contact.

Topics: Administration, Intranasal; Alginates; Animals; Brain; Brain Chemistry; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Female; Glucuronic Acid; Hexuronic Acids; Hyperglycemia; Insulin; Mice; Oxytocin; Pain; Particle Size; Phosphatidylcholines; Rats

The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients.. OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments.. During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile.. The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.

Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Down-Regulation; Female; Glycated Hemoglobin; Greece; Hospitals, University; Humans; Hyperglycemia; Male; Middle Aged; Obsessive-Compulsive Disorder; Outpatient Clinics, Hospital; Oxytocin; Psychiatric Status Rating Scales; Psychotic Disorders; Somatoform Disorders

Hypothalamic arginine-vasopressin (AVP) plays an important role both as a neurotransmitter and hormone in the regulation of blood glucose and feeding behavior. AVP-containing axons from the parvocellular subdivision of paraventricular nucleus of the hypothalamus terminate in the nucleus of the tractus solitarius (NTS), but the function of this projection is not known. Interestingly, the NTS also receives afferent information from the carotid body and other peripheral receptors involved in glucose homeostasis. We have previously reported that stimulation of the carotid body receptors initiates a hyperglycemic reflex and increases brain glucose retention. Here we show that direct administration of micro-doses of AVP into the NTS of anesthetized or awake rats rapidly increased the levels of blood glucose concentration and brain arterio-venous (A-V) glucose difference. This effect was not observed when the same doses of AVP were injected in the brainstem outside NTS. Arginine-vasopressin antagonist microinjections alone produced a small but significant reduction in brain A-V glucose. Pre-administered VP1-receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1),O-Me-Tyr(2),Arg(8)]vasopressin blocked the effects of AVP. These results indicate that AVP acting on its receptors locally within the NTS participates in glucose homeostasis, increasing both blood glucose concentration and brain A-V glucose differences. Hypothalamic AVP may facilitate hyperglycemic responses initiated by peripheral signals processed at the level of the NTS.

Topics: Animals; Arginine Vasopressin; Blood Glucose; Glucose; Homeostasis; Hormone Antagonists; Hyperglycemia; Male; Neural Pathways; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Solitary Nucleus

Local use of oxytocin-antibacterial complexes in combination with treatment of diabetes including divided insulinotherapy in patients with postinjection abscesses and non-insulin-dependent diabetes led to compensation of diabetes and earlier sanation of suppurative focus compared with patients treated by local antibiotics only.

Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chi-Square Distribution; Data Interpretation, Statistical; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Injections; Insulin; Middle Aged; Oxytocin

Topics: Adipose Tissue; Animals; Blood Glucose; Carbon Dioxide; Carbon Isotopes; Cricetinae; Diabetes Mellitus; Dogs; Female; Glucose; Hyperglycemia; Insulin; Male; Oxytocin; Pancreatectomy; Peptides; Pituitary Hormones, Posterior; Rats; Structure-Activity Relationship; Vasopressins; Vasotocin

Topics: Animals; Dogs; Glucose; Hyperglycemia; Hypoglycemia; Insulin; Lipid Metabolism; Metabolism; Oxytocin; Peptides; Rabbits; Vasopressins

Topics: Animals; Blood Glucose; Glucagon; Hyperglycemia; In Vitro Techniques; Oxytocin; Pituitary Hormones, Posterior; Poultry; Vasotocin

Topics: Animals; Blood; Dogs; Hyperglycemia; Insulin; Islets of Langerhans; Manometry; Oxytocin

Topics: Animals; Hyperglycemia; In Vitro Techniques; Liver; Oxytocin; Rats

Topics: Animals; Dogs; Fatty Acids; Fatty Acids, Nonesterified; Hyperglycemia; Hyperinsulinism; Oxytocin

Topics: Blood Glucose; Humans; Hyperglycemia; Oxytocics; Oxytocin

Topics: Arginine Vasopressin; Humans; Hyperglycemia; Oxytocics; Oxytocin; Vasopressins