Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the candidate genes that have been reviewed herein, adipsin, calcitonin, cholecystokin, Gi alpha and Gs subunits of G proteins, insulin I and II, and lipoprotein lipase have all been mapped to specific chromosomes in mouse or rat or both. In none of these cases is the chromosomal location syntenic with murine obesity genes db (on chromosome 4), or ob (on chromosome 6). Thus, all of these genes that code for metabolic modulators that are altered in obese animals but not in lean animals can be ruled out as possible loci of the primary genetic defect, at least for the murine models of obesity. In the case of neuropeptide Y, growth hormone, glucose transporter GLUT-4, the insulin receptor, and glyceraldehyde-3-phosphate dehydrogenase, chromosomal mapping has not yet been reported. However, in each of these cases, the evidence available strongly argues against any one of these physiologic modulators as the likely site of the primary defect for any one of the obesity mutations. Rather, in all of these cases, regardless of whether or not the gene has been mapped, the evidence suggests that posttranscriptional and/or post-translational processes are involved in bringing about the specific alterations in level or activity of the protein product that is seen in the obese animal. Often hormonal regulation is invoked as a possible explanation for the changes observed in gene expression. The hormones most commonly identified as having a mediating effect on the particular metabolic pathways involved are insulin and/or the adrenal glucocorticoids. Since in each of the obese mutants, circulating amounts of these hormones are elevated, severely so in the case of insulin, it would not be surprising to find that they influence the levels and activities of many protein products involved in a variety of central nervous system and peripheral metabolic pathways. Glucocorticoids are known to exert direct effects on gene expression; however, with respect to adipsin gene expression, a direct effect has not been found. Furthermore, insulin itself has been considered as a candidate for the genetic lesion in these animals and has been ruled out by chromosomal localization. Thus, while it may certainly prove to be the case that both insulin and glucocorticoids affect these systems in some way, their effects appear to be indirect. The work by Platt and colleagues in transgenic mice provides the first evidence of signal transduction between an obese mutant allele and the promoter sequence for a gene that shows significantly altered expression in the obese animal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Animal models of obesity: genetic aspects. 189 4

The manifestations of endocrine derangements in the musculoskeletal system in infancy and childhood are disturbances in growth and maturation and in adulthood are disturbances in maintenance and metabolism. Hypercortisolism during skeletal immaturity suppresses growth. In the adult, hypercortisolism leads to osteoporosis, osteonecrosis, and muscle wasting. Deficiency of growth hormone during skeletal development results in short stature. An excess of growth hormone in a skeletally immature individual results in gigantism, an excess in a skeletally mature individual results in acromegaly. Patients with gigantism have extreme height with normal body proportions. Musculoskeletal manifestations of acromegaly include soft-tissue thickening, vertebral body enlargement, characteristic hand and foot changes, and enthesal bony proliferation. Hyperthyroidism causes catabolism of protein and loss of connective tissue, which manifest as muscle wasting. Deficient levels of thyroid hormone cause defects in growth and development. Severe growth retardation from congenital hypothyroidism is rare because neonatal screening recognizes the disorder and leads to early treatment. The skeletal manifestation of hypergonadism in children is precocious growth and early skeletal maturation. Although the initial precocious growth spurt results in a tall child, early closure of the growth plates results in a short adult. Hypogonadism in the prepubertal child results in delayed adolescence and delayed skeletal maturation. Diabetes mellitus in childhood results in decreased growth, a phenomenon presumed to be secondary to nutritional abnormalities. Generalized osteoporosis and short stature are common. In the adult, generalized osteoporosis may accompany insulin-dependent diabetes mellitus if obesity is absent. Calcification of interdigital arteries of the foot is common in diabetics and uncommon in other conditions. Additional skeletal manifestations relate to complications of diabetes such as peripheral neuropathy and diabetic foot disease.
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PMID:Radiologic manifestations in the musculoskeletal system of miscellaneous endocrine disorders. 198 24

This paper examines the treatment of obesity, using a feedback model of nutrient regulation. A feedback model contains afferent signals and a central controller that transduces afferent information into efferent signals that modulate the controlled system. Using this model and the receptor hypothesis for drug action, a variety of current and potential therapeutic approaches are discussed. Among the more promising approaches would be cholecystokinin agonists, small molecules that mimic ketoacids, agonists to corticotropin-releasing hormone, beta-3 agonists, antagonists to opioid peptides, antagonists to neuropeptide Y, glucocorticoid receptor antagonists, and growth hormone agonists. Since a number of mechanisms can influence body fat and nutrient partitioning, it is likely that optimal therapy will involve use of more than one pharmacologic agent.
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PMID:Treatment for obesity: a nutrient balance/nutrient partition approach. 201 19

In this study we have examined the relationship between obesity and endocrine glands. We have underlined that obesity can be a symptom of some endocrine diseases and that, on the other side, only a few number of cases with excessive weight have a true endocrine pathogenesis. The endocrine implications of essential obesity, only detectable with appropriate dynamic tests, are sometimes expression of an altered peripheral metabolism. The more relevant hormonal data that we will examine in details are: increase of insulin plasma levels, altered hypothalamic neuroregulation with consequence on the gonadotropin secretion and values of prolactin, growth hormone and cortisol.
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PMID:[Obesity: relationships with the endocrine system]. 203 64

Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 micrograms iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 +/- 4 vs 44 +/- 16 micrograms/l; mean +/- SEM). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 +/- 5 vs 77 +/- 20 micrograms/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.
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PMID:Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects. 210 45

Nineteen women with polycystic ovarian disease (PCO; 9 obese) and 15 normal ovulatory women (7 obese) were studied at their follicular phase. All patients had an oral glucose tolerance test (OGTT) before and after treatment with gonadotropin-releasing hormone (GnRH) agonist (Buserelin 400 micrograms/die s.c. for 8 weeks) to investigate the relationship between ovarian steroidogenesis and insulin and growth hormone (GH) and insulin-like growth factor (SmC) secretion. Luteinizing hormone, follicle-stimulating, estradiol, androstenedione, testosterone, dehydroepiandrosterone sulfate, cortisol, insulin, GH and SmC were measured basally at the time of OGTT. PCO patients showed higher androgen basal levels than control patients. All subjects showed a normal glycemic response to OGTT. The mean fasting level and area under the curve of plasma insulin were also significantly greater in PCO than in control patients (p less than 0.05), while GH and SmC plasma concentrations did not differ between the groups. Despite a considerable decrease in androgens and the similar levels in both PCO and control women, buserelin treatment did not determine any significant changes of insulin and GH-SmC secretion. GH and SmC did not correlate with ideal body weight (IBW), insulin or androgens, whereas insulin correlated with both testosterone and androstenedione levels (p less than 0.05) and with IBW (p less than 0.01); after the buserelin regimen only IBW remained related to plasma insulin (p less than 0.01). In conclusion results of this study confirm that hyperinsulinism is a characteristic picture of PCO and is related in an unclear way with hyperandrogenism and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone and somatomedin-C secretion in patients with polycystic ovarian disease. Their relationships with hyperinsulinism and hyperandrogenism. 211 May 44

To determine whether impaired growth hormone (GH) secretion in obese subjects is a consequence of obesity or a pre-existing pituitary-hypothalamic disorder, we measured (1) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body weight [BW]), arginine (0.5 g/kg BW), and L-dopa (500 mg); and (2) plasma glucose, insulin, and free fatty acids (FFA) in obese subjects before and after weight reduction due to very-low-calorie diet therapy using Optifast (240 kcal/d for 8 to 12 weeks). Body weight and body mass index (BMI) values before and after weight reduction were 87.2 +/- 4.1 kg and 34.5 +/- 0.9 kg/m2, and 67.8 +/- 2.7 kg and 27.0 +/- 0.4 kg/m2, respectively. GH response to GRH, arginine, and L-dopa in obese subjects was markedly impaired before weight reduction, whereas significantly increased responses were noted after weight reduction (P less than .01). Impaired integrated GH response to GRH, arginine, and L-dopa in obese subjects was significantly restored after weight reduction (P less than .01). Plasma glucose levels did not change, while plasma insulin and FFA levels decreased significantly after weight reduction (P less than .01, P less than .05). There was no significant correlation between integrated GH response to these three stimuli and plasma levels of glucose, insulin, and FFA, respectively. The reversibility of GH response to all three stimuli after weight reduction suggests that impaired GH secretion is a consequence of obesity rather than a pre-existing pituitary-hypothalamic disorder.
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PMID:Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and L-dopa in obesity. 211 19

Lipid metabolism was studied in 16 acromegalic patients who all underwent transsphenoidal selective pituitary adenomectomy (SPA). Before the operation, their serum lipid levels correlated with none of the basal levels of serum growth hormone (GH), basal levels of plasma somatomedin-C (SM-C), fasting levels of plasma glucose (FPG), peak levels of plasma glucose (PGp) or basal and peak levels of serum immunoreactive insulin (IRIb and IRIp, resp.) in the oral glucose tolerance test (OGTT), and obesity indices. The serum GH levels as well as plasma SM-C levels in the group with decreased serum high density lipoprotein-cholesterol (HDL-C) differed greatly from those of the normal HDL-C group. However, there was no significant difference in either serum GH or plasma SM-C between groups with and without metabolic abnormality of any other lipid examined. After the operation, the basal levels of serum GH and plasma SM-C decreased significantly. In conjunction with these changes, PGp, serum IRIb, serum triglyceride (TG), non-esterified fatty acid (NEFA) and very low density lipoprotein (VLDL) decreased significantly. In contrast, serum HDL-C increased significantly. However, FPG, serum IRIp, obesity indices, serum total cholesterol (TC) and serum low density lipoprotein (LDL) showed no significant change. There were no significant differences in the levels of any serum lipid either before or after surgery among the diabetic, borderline and normal types defined by the preoperative OGTT patterns. Atherogenic indices (AIs) decreased significantly and returned to normal postoperatively. These results suggest that obesity or secondary diabetes is not a direct cause of hyperlipidemia in acromegaly. The prognosis of acromegaly is affected by arteriosclerotic complications. It is intriguing, therefore, that AIs were normalized by transsphenoidal SPA. Being rather a safe procedure, it can be performed without hesitation, aside from a conservative treatment.
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PMID:Lipid metabolism in acromegalic patients before and after selective pituitary adenomectomy. 212 1

IGF I and IGF II are insulin-like peptide hormones circulating in blood bound to specific carrier proteins. IGF I mediates many actions of growth hormone--hence its designation as somatomedin C--and it stimulates cell replication, cell differentiation and the synthesis of cellular products (matrix proteins, etc.). Recent investigations in normal human subjects show that pharmacological doses of IGF I increase renal function and have profound metabolic effects that might prove to be useful in the treatment of conditions characterized by relative insulin resistance, such as type 2 diabetes, obesity and hyperlipidemia.
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PMID:[Insulin-like growth factors (IGF I and IGF II) and diabetes]. 215 81

Endogenous factors cross-reacting with antidigoxin antibodies have been found in several tissues and body fluids of animals and humans, using commercially available digoxin radioimmunoassay or enzyme immunoassay methods. The chemical characteristics of these endogenous factors are, at present, unknown, although it has been suggested that they could be substances with low molecular weight. Experimental studies and theoretical considerations indicate that endogenous digitalis-like factors (DDLFs), in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, EDLF can be an endogenous modulator of the membrane sodium-potassium pump and several authors have suggested that EDLF could play a role in the regulation of fluids and electrolytes, muscular tone of myocardial and also in the pathogenesis of arterial hypertension. In this review, the authors discuss the hypothesis that, in metabolic diseases such as diabetes mellitus, obesity and acromegaly, the sodium retention and volume expansion, possibly due to exaggerated sodium intake, and/or exogenously induced peripheral hyperinsulinemia and high levels of growth hormone, could trigger a sustained release of EDLF, which in turn increases the blood pressure.
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PMID:Is the endogenous digitalis-like factor the link between hypertension and metabolic disorders as diabetes mellitus, obesity and acromegaly? 222 23


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