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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indices of plasma hypertonicity, elevated plasma concentrations of solutes that draw fluid out of cells by osmosis, are needed to pursue hypertonicity as a possible risk factor for obesity and chronic disease. This paper proposes a new index that may be more sensitive to mild hypertonicity in vivo at a point in time than traditional measures. The index compares mean corpuscular volume (MCV) estimates from diluted (in solution by automated cell counter) and nondiluted blood (calculated from manual hematocrit, MCV=Hct/RBC*10(6)). A larger Auto vs Manual MCV (>2 fl) in vitro indicates hypertonicity in vivo if the cell counter diluent is isotonic with the threshold for plasma vasopressin (PVP) release and PVP is detectable in plasma (>0.5 pg/ml). To evaluate this principle of concept, hypertonicity was induced by 24-h fluid restriction after a 20 ml/kg water load in four healthy men (20-46 years). Unlike serum and urine indices, the MCV difference-&-PVP index detected hypertonicity in all participants.
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PMID:A proposed method for assessing plasma hypertonicity in vivo. 1685 42

Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia.
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PMID:Hormone replacement therapy and vascular risk disorders in adult hypopituitarism. 1728 80

Arginine-vasopressin (AVP) is known to be involved in maintaining glucose homeostasis, and AVP-resistance is observed in poorly controlled non-insulin-dependent diabetes mellitus subjects, resulting in a lowered plasma volume. Recently we reported that V1a vasopressin receptor-deficient (V1aR(-/-)) mice exhibited a decreased circulating blood volume and hypermetabolism of fat accompanied with impaired insulin-signaling. Here we further investigated the roles of the AVP/V1a receptor in regulating glucose homeostasis and plasma volume using V1aR(-/-) mice. The plasma glucose levels at the baseline or during a glucose tolerance test were higher in V1aR(-/-) than wild-type (WT) mice. Moreover, a hyperinsulinemic-euglycemic clamp revealed that the glucose infusion rate was significantly lower in V1aR(-/-) mice than in WT mice and that hepatic glucose production was higher in V1aR(-/-) mice than WT mice. In contrast to the increased hepatic glucose production, the liver glycogen content was decreased in the mutant mice. These results indicated that the mutant mice had impaired glucose tolerance. Furthermore, feeding V1aR(-/-) mice a high-fat diet accompanied by increased calorie intake resulted in significantly overt obesity in comparison with WT mice. In addition, we found that the circulating plasma volume and aldosterone level were decreased in V1aR(-/-) mice, although the plasma AVP level was increased. These results suggested that the effect of AVP on water recruitment was disturbed in V1aR(-/-) mice. Thus, we demonstrated that one of the AVP-resistance conditions resulting from deficiency of the V1a receptor leads to decreased plasma volume as well as impaired glucose homeostasis, which can progress to obesity under conditions of increased calorie intake.
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PMID:Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. 1730 60

Genetic variation in G protein-coupled receptors (GPCRs) results in the disruption of GPCR function in a wide variety of human genetic diseases. In vitro strategies have been used to elucidate the molecular pathologies that underlie naturally occurring GPCR mutations. Various degrees of inactive, overactive, or constitutively active receptors have been identified. These mutations often alter ligand binding, G protein coupling, receptor desensitization, and receptor recycling. The role of inactivating and activating calcium-sensing receptor (CASR) mutations is discussed with respect to familial hypocalciuric hypercalemia (FHH) and autosomal dominant hypocalemia (ADH). Among ADH mutations, those associated with tonic-clonic seizures are discussed. Other receptors discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone, luteinizing hormone, gonadotropin-releasing hormone (GnRHR), adrenocorticotropic hormone, vasopressin, endothelin-beta, purinergic, and the G protein associated with asthma (GPRA). Diseases caused by mutations that disrupt GPCR function are significant because they might be selectively targeted by drugs that rescue altered receptors. Examples of drug development based on targeting GPCRs mutated in disease include the calcimimetics used to compensate for some CASR mutations, obesity therapeutics targeting melanocortin receptors, interventions that alter GnRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor in a rare bleeding disorder. The discovery of GPRA suggests that drug screens against variant GPCRs may identify novel drugs. This review of the variety of GPCRs that are disrupted in monogenic disease provides the basis for examining the significance of common pharmacogenetic variants.
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PMID:G protein-coupled receptors disrupted in human genetic disease. 1837 Feb 33

Sibutramine, a serotonin reuptake inhibitor, currently is used in treatment of obesity. The known side effects of sibutramine, ie, hypertension and tachycardia, depend on its adrenergic and serotoninergic effects. We describe a case of life-threatening hyponatremia associated with sibutramine use in an obese woman. We hypothesize that sibutramine, through its effect on neurotransmitters, may induce antidiuretic hormone secretion and lead to a syndrome of inappropriate antidiuretic hormone secretion. We advise careful monitoring of water-electrolytic balance during sibutramine therapy.
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PMID:Severe symptomatic hyponatremia during sibutramine therapy: a case report. 1902 58

Type 2 diabetes is associated with obesity, insulin resistance, hyperglycemia, hyperphagia, polyuria, body weight gain, excessive secretion of glucocorticoids (GCs), thymus involution, adrenal gland hypertrophy, diabetic nephropathy, etc. We examined the effect of cerebrocrast, a new antidiabetic agent (synthesized in the Latvian Institute of Organic Synthesis), on body weight, food and water intake, urine output, and on changes of organ weight: that is, kidney, thymus, adrenal gland of normal rats. Cerebrocrast was administered at doses of 0.05 and 0.5 mg kg(-1) per os (p.o.) once a day for three consecutive days, and its effects were observed from 3 to 27 days after the last administration. Cerebrocrast, during the experimental period, decreased body weight by an average of approximately 32.3%, food intake by about 10-15% at the beginning of the experiments and by 22.6% at the end of the experiments, especially at a dose of 0.5 mg kg(-1). Water intake and urine output in comparison with controls were decreased. The daily food intake decreased about 1.0 and 2.1 g by administering single cerebrocrast doses of 0.05 and 0.5 mg kg(-1) body weight (b.w.), respectively, but by administering for three consecutive days, food intake decreased by about 2.2 and 3.4 g, respectively. The weekly body weight gain decreased by administering a single dose of cerebrocrast by 2.61 and 2.51 g, respectively, and by triple administration it decreased by 4.36 and 3.07 g, respectively. Cerebrocrast has long-lasting effects on these parameters and on thymus and adrenal gland weight. As cerebrocrast decreased glucose levels in normal and streptozotocin (STZ)-induced diabetic rats, it also promoted glucose uptake by the brain, intensified insulin action and formation de novo of insulin receptors. We can conclude that cerebrocrast may regulate food intake and body weight through glucose sensing by proopiomelanocortin (POMC) neurons, that are involved in control of glucose homeostasis, stimulation of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion, activation of MC4-Rs and inhibition of neuropeptide Y (NPY) in the ARC of the hypothalamus, affecting the kidney, and causing decreased urine output and water intake. Moreover, it could stimulate secretion of vasopressin. By administration of cerebrocrast thymus mass was increased, thereby preventing the action of GCs. As cerebrocrast inhibited L- and T-type calcium channels, it can prevent vasoconstriction of kidney arterioles and aldosterone secretion that have significant roles in the development of hypertension and diabetic nephropathy. These properties of cerebrocrast are important for treatment of Type 2 diabetes and its consequent development of hypertension and diabetic nephropathy.
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PMID:Effect of cerebrocrast on body and organ weights, food and water intake, and urine output of normal rats. 1903 18

[Arg(8)]-vasopressin (AVP) is involved in the regulation of glucose homeostasis via vasopressin V(1A) and vasopressin V(1B) receptor. Our previous studies have demonstrated that vasopressin V(1A) receptor deficient (V(1A)R(-/-)) mice exhibited hyperglycemia, vasopressin V(1B) receptor deficient (V(1B)R(-/-)) mice, in contrast, exhibited hypoglycemia with hypoinsulinemia. These findings indicate that vasopressin V(1A) receptor deficiency results in decreased insulin sensitivity, whereas vasopressin V(1B) receptor deficiency results in increased insulin sensitivity. In our previous and present studies, we used the glucose tolerance test to investigate glucose tolerance in mutant mice, lacking either the vasopressin V(1A) receptor, the vasopressin V(1B) receptor, or both receptors, that were kept on a high-fat diet. Glucose and insulin levels were lower in V(1B)R(-/-) mice than in wild type (WT) mice when both groups were fed the high-fat diet, which indicates that the insulin sensitivity of the V(1B)R(-/-) mice was enhanced. V(1A)R(-/-) mice on the high-fat diet, on the other hand, exhibited overt obesity, along with an impaired glucose tolerance, while WT mice on the high-fat diet did not. Next, in order to assess the effect of vasopressin V(1B) receptor deficiency on the development of glucose intolerance caused by vasopressin V(1A) receptor deficiency, we generated mice that were deficient for both vasopressin V(1A) receptor and vasopressin V(1B) receptor (V(1AB)R(-/-)), fed them a high-fat diet, and examined their glucose tolerances using the glucose tolerance test. Glucose tolerance was impaired in V(1AB)R(-/-) mice, suggesting that the effects of vasopressin V(1B) receptor deficiency could not influence the development of hyperglycemia promoted by vasopressin V(1A) receptor deficiency, and that blockade of both receptors could lead to impaired glucose tolerance.
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PMID:Both V(1A) and V(1B) vasopressin receptors deficiency result in impaired glucose tolerance. 1937 19

An anorexigenic peptide, nesfatin-1 was found in rat hypothalamus, and its expression in the paraventricular nucleus of the hypothalamus was reduced by starvation. Intracerebroventricular administration dose-dependently inhibited food intake for 6 h in male Wistar and leptin resistant, Zucker fatty rats. There may be a crosstalk between nesfatin-1 pathway and melanocortin pathway in the brain. Nesfatin-1 neurons co-express with oxytocin, vasopressin and melanin concentrating hormone in the hypothalamus. Intraperitoneal administration of nesfatin-1 and its mid-segment dose-dependently inhibited food intake for 3 h. Mid-segment of nesfatin-1 decreased food intake under leptin-resistant animal models of obesity. Intraperitoneal administration of the mid-segment of nesfatin-1 increased proopiomelanocortin and cocain- and amphetamine-related peptide mRNA expression in the nucleus of the solitary tract, but not in arcuate nucleus of the hypothalamus. In this review, we summarized recent progress in the research about the possible mechanism of nesfatin-1-induced anorexia.
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PMID:A new anorexigenic protein, nesfatin-1. 1945 36

The article critically reviews selected, clinically significant, adverse endocrine and metabolic effects associated with psychotropic drug treatments, including hyperprolactinaemia, hyponatraemia, diabetes insipidus, hypothyroidism, hyperparathyroidism, sexual dysfunction and virilization, weight loss, weight gain and metabolic syndrome (type 2 diabetes mellitus, dyslipidaemia and hypertension). Such effects are prevalent and complex, but can be managed clinically when recognized. They encourage continued critical assessment of benefits versus risks of psychotropic drugs and underscore the importance of close coordination of psychiatric and general medical care to improve long-term health of psychiatric patients. Options for management of hyperprolactinaemia include lowering doses, switching to agents such as aripiprazole, clozapine or quetiapine, managing associated osteoporosis, carefully considering the use of dopamine receptor agonists and ruling out stress, oral contraceptive use and hypothyroidism as contributing factors. Disorders of water homeostasis may include syndrome of inappropriate antidiuretic hormone (SIADH), managed by water restriction or slow replacement by hypertonic saline along with drug discontinuation. Safe management of diabetes insipidus, commonly associated with lithium, involves switching mood stabilizer and consideration of potassium-sparing diuretics. Clinical hypothyroidism may be a more useful marker than absolute cut-offs of hormone values, and may be associated with quetiapine, antidepressant and lithium use, and managed by thyroxine replacement. Hyper-parathyroidism requires comprehensive medical evaluation for occult tumours. Hypocalcaemia, along with multiple other psychiatric and medical causes, may result in decreased bone density and require evaluation and management. Strategies for reducing sexual dysfunction with psychotropics remain largely unsatisfactory. Finally, management strategies for obesity and metabolic syndrome are reviewed in light of the recent expert guidelines, including risk assessment and treatments, such as monoamine transport inhibitors, anticonvulsants and cannabinoid receptor antagonists, as well as lifestyle changes.
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PMID:Adverse endocrine and metabolic effects of psychotropic drugs: selective clinical review. 1995 39

The constant supply of oxygen and nutriments to cells (especially neurons) is the role of the cardiovascular system. The constant supply of water (and sodium) for cardiovascular function is the role of thirst and sodium appetite and kidney function. This physiological regulation ensures that plasma volume and osmolality are maintained within set limits by initiating behaviour and release of hormones necessary to ingest and conserve water and sodium within the body. This regulation is separated into 2 parts; intracellular and extracellular (blood). An increased osmolality draws water from cells into the blood thus dehydrating specific brain osmoreceptors that stimulate drinking and release of anti diuretic hormone (ADH or vasopressin). ADH reduces water loss via lowered urine volume. Extracellular dehydration (hypovolaemia) stimulates specific vascular receptors that signal brain centres to initiate drinking and ADH release. Baro/volume receptors in the kidney participate in stimulating the release of the enzyme renin that starts a cascade of events to produce angiotensin II (AngII), which initiates also drinking and ADH release. This stimulates also aldosterone release which reduces kidney loss of urine sodium. Both AngII and ADH are vasoactive hormones that could work to reduce blood vessel diameter around the remaining blood. All these events work in concert so that the cardiovascular system can maintain a constant perfusion pressure, especially to the brain. Even if drinking does not take place ADH, AngII and aldosterone are still released. Furthermore, it has been observed that treatment of hypertension, obesity, diabetes and cancer can involve renin-AngII antagonists which could suggest that, in humans at least, there may be dysfunction of the thirst regulatory mechanism.
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PMID:Thirst and hydration: physiology and consequences of dysfunction. 2021 37


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