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

Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been demonstrated experimentally: binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.
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PMID:Abnormal production of androgens in women with breast cancer. 784 May 9

Although the growth-promoting effects of insulin-like growth factor II (IGF-II) have been intensively studied, the acute actions of this hormone on glucose metabolism have been less well evaluated, especially in skeletal muscle of humans. We and other groups have shown that IGFs reduce glycaemic levels in humans and stimulate glucose uptake in rat muscle. The purpose of the present study was to evaluate the effect of IGF-II on glucose transport in muscle of normal and obese patients with and without non-insulin-dependent diabetes mellitus (NIDDM), as well as to identify the receptor responsible for this action. 2-Deoxyglucose transport was determined in vitro using a muscle-fibre strip preparation. IGF-II were investigated in biopsy material of rectus abdominus muscle taken from lean and obese patients and obese patients with NIDDM at the time of surgery. In the lean group, IGF-II (100 nM) stimulated glucose transport 2.1-fold, which was slightly less than stimulation by insulin (2.8-fold) at the same concentration. Binding of IGF-II was approx. 25% of that of insulin at 1 nM concentrations of both hormones. Obesity with or without NIDDM significantly reduced IGF-II-stimulated glucose uptake compared with the lean group. In order to explore which receptor mediated the IGF-II effect, we compared glucose uptake induced by IGF-II and two IGF-II analogues: [Leu27]IGF-II, with high affinity for the IGF-II/Man 6-P receptor but markedly reduced affinity for the IGF-I and insulin receptors, and [Arg54,Arg55]IGF-II was similar to that of IGF-II, whereas [Leu27]IGF-II had a very diminished effect. Results show that IGF-II is capable of stimulating muscle glucose uptake in lean but not in obese subjects and this effect seems not to be mediated via an IGF-II/Man 6-P receptor.
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PMID:Stimulation of glucose uptake by insulin-like growth factor II in human muscle is not mediated by the insulin-like growth factor II/mannose 6-phosphate receptor. 801 Sep 60

Childhood obesity may be characterised by basal and reactive hyperinsulinemia, reduced growth hormone (HGH) responses to various provocative stimuli and increased plasma concentration of somatomedine-C/insulin-like growth factor-I (SM-C/IGF-I). For this reason the relationship between the degree of obesity (i. e. BMI), serum immunoreactive insulin (IRI) and plasma SM-C/IGF-I was investigated in children with obesity (n = 26, age: 13.0 +/- 0.97 years, BMI: 32.8 +/- 5.3 kg/m2). SM-C/IGF-I was increased in obese children compared to the normal range of this age. Significant positive correlations were found between BMI and IRI, between BMI and SM-C/IGF-I, and between IRI and SM-C/IGF-I. These results suggest that SM-C/IGF-I production in obesity is regulated by IRI dependent on BMI and this regulating effect of insulin may be important in obesity since HGH production to provocative stimuli is reduced.
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PMID:[Relationship between immunoreactive insulin and plasma somatomedin-C/insulin-like growth factor-I concentration in childhood obesity]. 806 41

We have shown that maximally stimulated glucose transport is reduced in in vitro incubated muscle of morbidly obese subjects. To investigate the possibility that a "threshold" of obesity exists, above which glucose transport is significantly decreased, hormone (insulin, IGF-I, or IGF-II) stimulation of glucose transport was correlated with body mass index using muscle biopsies from a group of 30 lean to obese females with BMI ranging from 16 to 40. There was a significant negative relationship between stimulation for glucose transport and BMI (R = 0.765). These data suggest there is no obesity threshold for insulin resistance in skeletal muscle but a continuous decline in glucose transport below a BMI of approximately 30 kg/m2, after which insulin and the IGFs no longer stimulate glucose transport.
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PMID:Effect of moderate obesity on glucose transport in human muscle. 808 71

Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10(-7) M GHRH elicited a significantly lower GH secretion from the pituitaries of obese male rats but induced a similar GH secretion from the pituitaries of lean and obese female rats. In these pituitaries, GH concentration was similar in obese versus lean male and female rats [corrected]. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-I) were evaluated. Obese male rats had lower IGF-I concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone secretion is differently affected in genetically obese male and female rats. 810 99

Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.
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PMID:Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity? 834 45

Growth hormone secretion is blunted in obesity. Recent studies have shown that the sub-group of obesity with preponderance of accumulation of fat in visceral depots is associated with endocrine abnormalities. We therefore measured IGF-I concentrations in serum in 27 men who also underwent computerized tomography measurements of regional and total body fat mass. Furthermore, euglycemic-hyperinsulinemic glucose clamps were used to determine insulin resistance, and established 'risk factors' for cardiovascular disease and non-insulin dependent diabetes mellitus were measured, i.e. blood pressure, plasma lipids, and blood glucose, as well as sex steroid hormones. Visceral fat mass systolic blood pressure and triglycerides were higher (P < 0.05) in the group with low (87 +/- 4 micrograms/l) IGF-I values, compared to those with high (126 +/- 6 micrograms/l) IGF-I values, divided after the median value. IGF-I was negatively correlated with visceral fat mass (r = 0.40), independently of subcutaneous and total fat mass. As described before visceral fat mass was directly associated to a majority of the measured 'risk factors', as well as indirectly to testosterone and sex hormone binding globulin (SHBG) concentrations. The latter were also strongly related statistically to the 'risk factors'. IGF-I concentrations showed, however, weaker correlations with the metabolic factors, blood pressure or sex steroid hormones. Multivariate analyses revealed that the correlations of visceral fat with the risk factors were not influenced by IGF-I, while testosterone or SHBG totally abolished these associations. The results indicate that low serum IGF-I concentrations, suggesting deficient growth hormone secretion, are associated with visceral but not with subcutaneous or total fat masses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low concentrations of insulin-like growth factor-I in abdominal obesity. 838 69

Normal human ageing is associated with changes in body composition which include a decrease in muscle mass and strength, bone mass loss and increase in adipose mass. A physiological decrease in growth hormone (GH) and IGF-I secretion accompanies these changes. Many of the physiological changes that accompany normal human ageing are very similar to those found in GH deficient patients. Nevertheless, responsiveness to exogenous administered GH persists with advancing age. GH administration to elderly individuals has produced an decrease in fat mass and an increase in lean body mass, being this finding consistent with the hypothesis that GH deficiency could be a contributing cause to senescent changes in some elderly individuals. GH treatment has also been used with encouraging results in adult subjects with isolated or combined GH deficiency. On the other hand, several clinical studies have recently shown the efficiently of GH treatment on diverse pathological processes such as severe catabolic states (surgery, sepsis, trauma, buns), osteoporosis, diabetic ulcers and obesity. The most frequent side effects are sodium and water retention, impairment in glucose tolerance and carpal tunnel syndrome, although in general the treatment has been well tolerated. The clear definition of the therapeutical applications of GH in the adult warrants further clinical investigation.
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PMID:[New physiological and pharmacological aspects of the growth hormone (II). Therapeutic applications in adults]. 849 41

We describe a new animal model of obesity and GH deficiency and report the effects on body fat of administering (GH) and insulin-like growth factor (IGF-I) in the model. Female GH-deficient dwarf rats fed a high-fat diet became obese and insulin-resistant compared with chow-fed controls. They were treated with recombinant human GH (rhGH 100-500 micrograms/day, s.c. for 14 days) by daily injection or minipump infusion with or without rhIGF-I (200 micrograms/day, sc infusion). Injections of rhGH increased body weight; infusions of rhGH caused weight loss. RhIGF-I by itself, or rhIGF-I plus GH injections had little effect, whereas rhGH infusions plus rhIGF-I caused a weight loss equivalent to the weight gained during the high-fat feeding and a decrease in fat pad weight. For some responses (serum IGF-1 and GHBP), the obese rats were GH resistant. Fat was lost from the internal fat pads when obese rats were returned to a chow diet, and injections of rhGH surprisingly attenuated this loss of fat. In obese dwarf rats, the lipolytic effects of rhGH are dose-regime dependent. By itself IGF-I is not insulin-like, but in the presence of GH it has antiinsulin actions causing a powerful net lipolysis. If GH plus IGF-I have similar effects in humans they may be useful for reducing body fat.
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PMID:The obese growth hormone (GH)-deficient dwarf rat: body fat responses to patterned delivery of GH and insulin-like growth factor-I. 861 30

Lipase inhibition, leading to decreased intestinal fat adsorption can be used in the treatment of obesity. Orlistat, a lipase inhibitor, in a dose of 50 mg three times a day leads to a significant increase in weight loss compared to placebo in moderately obese people. These results are confirmed in a multiple-dose study using 10 mg, 60 mg and 120 mg Orlistat three times a day vs. placebo. The use of lipase inhibition has no significant influence on fasting levels of several hormonal systems, including thyroid hormones, catecholamines and IGF-I. The same is true for the responses of several gastrointestinal and pancreatic hormones after a liquid high-fat mixed meal. In general, Orlistat is tolerated very well, although a higher occurrence of gastrointestinal side effects is seen.
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PMID:First clinical studies with orlistat: a short review. 869 67


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