oxytocin and Diabetes-Mellitus

Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.

Topics: Amenorrhea; Animals; Anorexia Nervosa; Autocrine Communication; Bone and Bones; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Cognitive Dysfunction; Diabetes Mellitus; Estrogens; Female; Humans; Male; Osteoporosis, Postmenopausal; Oxytocin; Paracrine Communication; Sex Characteristics

Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs.

Topics: Animals; Cardiotonic Agents; Diabetes Mellitus; Exercise; Humans; Mice; Models, Theoretical; Myocardium; Obesity; Oxidative Stress; Oxytocin; Rats; Signal Transduction

Oxytocin (OXT) is a neurohypophysial hormone which is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. OXT is currently attracting considerable attention because it has been discovered that it regulates various functions of behavior especially in the context of social interactions. OXT is a key component in bone formation, glycemia, male sexuality, cardiac differentiation and pregnancy and thus it is important to be further explored. The authors review various aspects of gestational diabetes, including definition, screening, diagnostic procedures, complications, clinical evaluation, indications of delivery and neonatal aspects. Not only the relation among diabetes mellitus, oxytocin and neurophysiology concerning erectile dysfunction, but also the role of OXT in the activity of arginine and vasopressin is investigated. It is imperative to develop technological and experimental methods that will be able to reveal the oxytocin and its potential.

Topics: Animals; Arginine Vasopressin; Brain Chemistry; Diabetes Mellitus; Female; Gastric Emptying; Humans; Hypothalamus; Labor, Obstetric; Lactation; Male; Oxytocics; Oxytocin; Pregnancy; Rats; Receptors, Cell Surface; Receptors, Oxytocin; Social Behavior

Is oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein-coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo-pituitary-adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca²(+) in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy.

Topics: Affect; Analgesics; Animals; Brain; Diabetes Mellitus; Humans; Mental Disorders; Neoplasms; Osteoarthritis; Oxytocin; Receptors, Oxytocin; Sexual Dysfunction, Physiological; Signal Transduction; Social Behavior

Disruptions of the hypothalamic-pituitary axis can cause an arginine vasopressin deficiency, also known as central diabetes insipidus. Patients with this condition are at high risk of additional oxytocin deficiency owing to the close anatomical proximity of oxytocin-producing neurons; however, no conclusive evidence for such a deficiency has been reported. We aimed to use 3,4-methylenedioxymethamphetamine (MDMA, also known as ecstasy), a strong activator of the central oxytocinergic system, as a biochemical and psychoactive provocation test to investigate oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus).. This single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial included patients with arginine vasopressin deficiency (central diabetes insipidus) and healthy controls (matched 1:1 by age, sex, and BMI) and was conducted at the University Hospital Basel, Basel, Switzerland. We used block randomisation to assign participants to receive either a single oral dose of MDMA (100 mg) or placebo in the first experimental session; patients received the opposite treatment at the next session, with a wash-out period of at least 2 weeks between the two sessions. Participants and investigators assessing the outcomes were masked to assignment. Oxytocin concentrations were measured at 0, 90, 120, 150, 180, and 300 min after MDMA or placebo. The primary outcome was the area under the plasma oxytocin concentration curve (AUC) after drug intake. The AUC was compared between groups and conditions using a linear mixed-effects model. Subjective drug effects were assessed throughout the study using ten-point visual analogue scales. Acute adverse effects were assessed before and 360 min after drug intake using a 66-item list of complaints. This trial is registered with ClinicalTrials.gov, NCT04648137.. Between Feb 1, 2021, and May 1, 2022, we recruited 15 patients with arginine vasopressin deficiency (central diabetes insipidus) and 15 healthy controls. All participants completed the study and were included in the analyses. In healthy controls, median plasma oxytocin concentration was 77 pg/mL (IQR 59-94) at baseline and increased by 659 pg/mL (355-914) in response to MDMA, resulting in an AUC of 102 095 pg/mL (41 782-129 565); in patients, baseline oxytocin concentration was 60 pg/mL (51-74) and only slightly increased by 66 pg/mL (16-94) in response to MDMA, resulting in an AUC of 6446 pg/mL (1291-11 577). The effect of MDMA on oxytocin was significantly different between groups: the AUC for oxytocin was 82% (95% CI 70-186) higher in healthy controls than in patients (difference 85 678 pg/mL [95% CI 63 356-108 000], p<0·0001). The increase in oxytocin in healthy controls was associated with typical strong subjective prosocial, empathic, and anxiolytic effects, whereas only minimal subjective effects were observed in patients, in agreement with the lack of increase in oxytocin concentrations. The most frequently reported adverse effects were fatigue (eight [53%] healthy controls and eight [53%] patients), lack of appetite (ten [67%] healthy controls and eight [53%] patients), lack of concentration (eight [53%] healthy controls and seven [47%] patients), and dry mouth (eight [53%] healthy controls and eight [53%] patients). In addition, two (13%) healthy controls and four (27%) patients developed transient mild hypokalaemia.. These findings are highly suggestive of clinically meaningful oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus), laying the groundwork for a new hypothalamic-pituitary disease entity.. Swiss National Science Foundation, Swiss Academy of Medical Sciences, and the G&J Bangerter-Rhyner Foundation.

Topics: Arginine; Case-Control Studies; Cross-Over Studies; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Double-Blind Method; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Oxytocin

Oxytocin is released in response to a fatty meal. Blockage of the oxytocin receptor led to slower gastric emptying whereas stimulation resulted in less satiety in healthy volunteers. Patients with diabetes mellitus and gastroparesis lack oxytocin elevation, and dyspepsia is partly caused by reduced fundus accommodation causing early satiety and related symptoms. The aim of this study was thus to examine the effect of oxytocin on gastric emptying, satiety and volume intake in patients with gastrointestinal pathology.. Gastric emptying scintigraphy was performed twice in 12 patients with diabetic gastroparesis, once with oxytocin and once with saline as intravenous infusions. The patients scored their sensation of satiety using a visual analogue scale (VAS). The gastric emptying in patients with gastroparesis was prolonged during oxytocin infusion (p = 0.034) without affecting satiety. A slow satiety drinking test was performed in 14 patients with functional dyspepsia. The patients scored their satiety every five minutes until maximal satiety was reached, and the total volume was determined. The VAS was also completed 30 minutes afterwards. The test was performed twice, once with oxytocin and once with saline as intravenous infusions. There was no difference in satiety scores or volume of nutrient intake between saline and oxytocin infusions, either before, during or after the meal.. Oxytocin prolongs gastric emptying in patients with diabetes mellitus and gastroparesis, but has no effect on volume of nutrient intake or satiety and other related symptoms in patients with functional dyspepsia.

Topics: Adolescent; Adult; Area Under Curve; Diabetes Mellitus; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Infusions, Intravenous; Male; Meals; Middle Aged; Oxytocin; Satiation; Satiety Response; Sodium Chloride; Stomach; Tomography, Emission-Computed

Topics: Arginine; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Humans; Oxytocin

Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.

Topics: Animals; Diabetes Mellitus; Gene Expression; Hypothalamus; Inflammation; Linoleic Acid; Male; Mice; Nervous System Diseases; Obesity; Oxytocin; Soybean Oil; Stigmasterol

Protease inhibition has led to treating many diseases and has been successful in producing many commercial drugs by pharmaceutical companies. Among many proteases, serine protease has been attractive in treating metabolic disorder diabetes mellitus (DM). Gliptins have been proven to inhibit dipeptidyl peptidase-4 (DPP4), a serine protease, and are an emerging therapeutic drug target to reduce blood glucose levels, but until now there is no natural cyclic peptide proven to inhibit serine protease DPP4. This study demonstrates the potential mechanism of natural cyclic peptide oxytocin (OXT) as a DPP4 inhibitor. To achieve this, initially, activity atlas and field-based models of DPP4 inhibitors were utilized to predict the possible features of positive and negative electrostatic, hydrophobic, and activity shapes of DPP4 inhibition. Oxytocin binding mode, flexibility, and interacting residues were studied using molecular docking simulations studies. 3D-RISM calculations studies revealed that the stability of water molecules at the binding site are favorable. Finally, an experimental study using fluorescence assay revealed OXT inhibits DPP4 in a concentration-dependent manner in a significant way (

Topics: Animals; Diabetes Mellitus; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Molecular Docking Simulation; Oxytocin; Peptides, Cyclic; Protein Binding

The prevalence of births worldwide complicated by diabetes mellitus is increasing. In the UK, for example, <25% of diabetic women have a non-instrumental vaginal delivery. Strikingly, more than half the Caesarean sections (CS) in these patients are non-elective, but the reasons for this are not understood. We have tested the hypothesis that poor myometrial contractility as a consequence of the disease contributes to this high CS rate.. We compared spontaneous, high K depolarisation and oxytocin-induced contractions from diabetic and matched control patients having an elective CS. To investigate the mechanism of any differences we measured intracellular Ca, and performed western blotting and compared the tissues histologically.. There was significantly decreased contraction amplitude and duration in uteri from diabetic compared with control patients, even when possible confounders such as BMI were analysed. Reduced intracellular calcium signals and expression of calcium entry channels were found in uteruses from diabetic patients, which, along with a reduction in muscle content found on histological examination, could explain the reduced force. Myometrium from diabetic patients was responsive to oxytocin, but still did not reach the levels found in non-diabetic patients.. These are the first data investigating myometrium in diabetic patients and they support the hypothesis that there is poorer contractility even in the presence of oxytocin. The underlying mechanism is related to reduced Ca channel expression and intracellular calcium signals and a decrease in muscle mass. We conclude that these factors significantly contribute to the increased emergency CS rate in diabetic patients.

Topics: Adult; Body Mass Index; Calcium; Calcium Channels; Cesarean Section; Diabetes Complications; Diabetes Mellitus; Diabetes, Gestational; Female; Humans; Oxytocin; Pregnancy; Pregnancy Complications; Signal Transduction; Uterine Contraction

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

The aim of this study was to investigate the effect of oxytocin induction and augmentation on neonatal bilirubin levels in newborns of diabetic and hypertensive mothers. All women included in the study were admitted to the obstetrics department at Al Hussein Hospital. They were 18-38 years old, and their gestational ages were 38-41 weeks by date. A total number of 140 newborn infants were divided into 3 groups and studied for bilirubin levels. The first group consisted of 40 infants of diabetic mothers, 20 of whom were given oxytocin for labor induction and 20 of whom received it for labor augmentation. The second group consisted of 40 infants of hypertensive mothers, 20 of whom were given oxytocin for labor induction and 20 of whom received it for labor augmentation. The third group consisted of 60 controls, 20 of whom were given oxytocin for labor induction, 20 of whom received it for labor augmentation, and 20 of whom received no oxytocin. It was found that total and unconjugated bilirubin levels were higher in infants delivered after induction of labor, whether their mothers were diabetic, hypertensive, or neither, than in infants delivered without labor induction. Bilirubin levels were mildly high in infants of diabetic mothers after augmented delivery and then nullified after 24 hours. However, the study suggested that the increased bilirubin levels were related to induced labor rather than the medical problem of the mothers, provided that the newborns were of average weight.

Topics: Africa; Africa, Northern; Biology; Blood; Case-Control Studies; Delivery, Obstetric; Demography; Developing Countries; Diabetes Mellitus; Disease; Egypt; Endocrine System; Hormones; Hyperbilirubinemia; Hypertension; Middle East; Oxytocin; Physiology; Pituitary Hormones; Population; Population Characteristics; Pregnancy; Pregnancy Outcome; Reproduction; Research; Vascular Diseases; Women

Complete cDNA sequences for the vasopressin and oxytocin precursor polyproteins have been determined for the rat, calf, human and pig (vasopressin only), indicating the essential conservation of the precursor structures throughout mammals. DNA probes specific for vasopressin or oxytocin mRNAs have been used to identify both classic (hypothalamic) and novel (thymus, corpus luteum, phaeochromocytoma) sites of hormone expression. Semiquantitative DNA/RNA hybridization suggests that in rats expression of the vasopressin and oxytocin genes is positively effected by osmotic stress, negatively by a systemically applied excess of vasopressin; in the latter experiment a reduction in the hypothalamic levels of vasopressin and oxytocin mRNAs in normal and Brattleboro rats have been observed. This suggests a feedback regulation by the hormone as a possible element in controlling the transcription of the vasopressin gene.

Topics: Animals; Base Sequence; Cattle; Diabetes Mellitus; DNA; Female; Gene Expression Regulation; Humans; In Vitro Techniques; Oxytocin; Rats; RNA, Messenger; Species Specificity; Swine; Vasopressins

The paraventricular nucleus of the rat hypothalamus has been shown to project to the medulla and spinal cord. The proportion of oxytocin-neurophysin (OTNP) axons to vasopressin-neurophysin (VPNP) axons in these structures is unknown. A major difficulty in resolving this problem in previous immunocytochemical studies was the lack of a specific antiserum to each rat neurophysin. In this study two approaches have been used: (1) comparison of immunostaining for neurophysin in normal versus homozygous Brattleboro rats with diabetes insipidus (HODI) which lack VPNP, and (2) application of an antiserum to both rat neurophysins absorbed with HODI rat hypothalamic-pituitary extracts which contain only OTNP. The latter would result in an antiserum specific for VPNP. Our results indicate that the axons which constitute the caudal projections from the paraventricular nucleus are predominately oxytocinergic, the vasopressinergic innervation being limited to the nucleus tractus solitarius, the dorsal motor nucleus of vagus, and the substantia gelatinosa. A similar number of reactive fibers were seen in the medulla and spinal cord of normal and HODI rats. No positive perikarya were observed caudal to the hypothalamus. Fibers in the medulla appeared to terminate in the nucleus of the solitary tract and in the dorsal motor nucleus of the vagus nerve. Positive fibers throughout the cord were present in the substantia gelatinosa and in the intermediolateral grey. The possible role(s) of these projections in integrating autonomic functions and afferent information with neuroendocrine regulation is discussed.

Topics: Animals; Axons; Diabetes Insipidus; Diabetes Mellitus; Hypothalamus; Immunoenzyme Techniques; Medulla Oblongata; Neural Pathways; Neurophysins; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Receptors, Cell Surface; Spinal Cord; Staining and Labeling; Vasopressins

Topics: Angiotensin II; Animals; Diabetes Mellitus; Epinephrine; Fatty Acids, Nonesterified; Glucagon; Glucose; Glycerides; Hormones; Insulin; Liver; Liver Glycogen; Nucleotides, Cyclic; Obesity; Oxytocin; Parathyroid Hormone; Protein Kinases; Starvation; Stress, Physiological; Vasopressins

The objective of management in the pregnant diabetic patient is to achieve physiologic glucose homeostasis through the use of diet and insulin. As outlined, the numerous ancillary tests developed during the past 15 years to assist the clinician in determining impending fetal death have left much to be desired, especially where metabolic homeostasis has not been achieved prior to the thirty-sixth week of gestation. The statistics from this institution indicate that the maintenance of the plasma glucose concentration below 100 mg. per cent throughout gestation, regardless of the severity of the diabetes, all but removes the risk of maternal-fetal complications due to diabetes. The management is uniform for all patients exhibiting an abnormality of carbohydrate metabolism, and, although it is rather difficult to accept, there have been minimal neonatal complications when the protocol outlined in this presentation has been followed.

Topics: Adolescent; Adult; Amniotic Fluid; Blood Glucose; Child; Diabetes Mellitus; Female; Fetal Distress; Glucose; Humans; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Oxytocin; Placental Lactogen; Pregnancy; Pregnancy in Diabetics; Ultrasonography

Topics: Animals; Diabetes Insipidus; Diabetes Mellitus; Drinking Behavior; Female; Heterozygote; Homozygote; Hypothalamus; Male; Oxytocin; Pituitary Gland; Rats; Renin; Sex Factors; Urine; Vasopressins

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: Abruptio Placentae; Diabetes Mellitus; Drug Therapy; Female; Fetal Death; Humans; Labor, Induced; Oxytocin; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy, Prolonged; Rh-Hr Blood-Group System

Topics: Diabetes Mellitus; Estradiol; Female; Fetal Death; Humans; Infusions, Intravenous; Infusions, Parenteral; Oxytocin; Pharmacology; Pregnancy; Pregnancy in Diabetics; Progesterone; Relaxin; Uterus

Topics: Animals; Diabetes Mellitus; Dogs; Fatty Acids; Fatty Acids, Nonesterified; Humans; Oxytocics; Oxytocin; Plasma

Topics: Adrenalectomy; Diabetes Mellitus; Female; Humans; Insulin Antagonists; Lactation; Oxytocin