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

During the past decade, it became obvious that in contrast to defective insulin secretion in type I diabetes, defective insulin action (insulin resistance) is the most pertinent feature of type II diabetes. In addition, it has been known for a long time that obesity and insulin resistance are closely linked. Recently, hypertension also has been shown to often coincide with insulin resistance, although any causal relationships are still hypothetical. Last, several widely used pharmacological drugs such as diuretics, adrenergic blockers, and angiotensin-converting enzyme inhibitors may influence insulin sensitivity. Therefore, growing interest has emerged to most accurately measure insulin sensitivity. Although considerable knowledge has accumulated as to the actual mechanisms of insulin-dependent glucose transport, the signal transduction pathway of insulin remains poorly understood. When insulin sensitivity is measured, it is the overall glucose uptake that is quantified under controlled conditions. Other actions of insulin, such as the transport of ions, (e.g., sodium and potassium), synthesis of insulin-like growth factor-binding proteins, translocation of transporter proteins, and regulation of enzyme activities, are much more difficult to quantify. Of the many approaches used to quantify insulin action, the euglycemic hyperinsulinemic clamp technique has emerged as the most reliable tool, fulfilling clinical and scientific demands equally. In combination with tracer methodology and calorimetry, a detailed view into the quantitative aspects of insulin action at different target cells is possible. Whether insulin resistance extends to other known actions of insulin in addition to those on glucose metabolism remains open to debate.
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PMID:Determination of insulin sensitivity: methodological considerations. 128 39

Clinical and epidemiologic evidence has shown acanthosis nigricans to be closely related to defective tissue utilization of insulin in a number of previously recognized (e.g., obesity, lipodystrophy, and leprechaunism) as well as recently characterized (e.g., type A and type B syndromes) disorders. This article reviews the relationship of acanthosis nigricans to these insulin-resistant states. It also focuses attention on the possibility that interaction between excessive amounts of circulating insulin with insulin-like growth factor receptors on keratinocytes and dermal fibroblasts leads to the development of acanthosis nigricans.
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PMID:Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. 131 28

Normative age- and gender-related changes in body composition, serum lipids, testosterone, and insulin-like growth factor (IGF-1) were examined in the Cayo Santiago free-ranging rhesus macaques. In both adult males and females, body weights, crown-rump lengths, and circumference of the limbs were lowest in the oldest group (20+ years of age) as compared with other adult age classes. Body fat, as reflected in subcutaneous fatfold thickness and waist/thigh ratios, were higher in adult females than adult males. This gender dimorphism was first detectable among the 6-9 year old age group. Greatest body fat among females was observed in the 10-14 age group, whereas in males the highest values were observed in the 15-19 age group. Differences in body composition were also observed with respect to reproductive status. Although there were no gender differences in overall cholesterol levels, there were age-related differences between males and females, and only in males were cholesterol values positively related to adiposity. There were no age- or gender-related differences in triglyceride values, but levels were significantly higher in pregnant females in comparison with other reproductive states. Levels of testosterone were not significantly related to any morphometric parameter and values did not decrease significantly with age. Levels of IGF-1 exhibited a significant age-related decrease among adult males, and females had higher levels independent of age. The similarities between the present findings and human studies suggest that further studies in the free-ranging rhesus macaques would provide a bridge between studies of laboratory-housed primates and studies of human beings with respect to the etiology of obesity and life-history changes in body composition and endocrine and metabolic parameters.
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PMID:Age- and gender-related changes in body size, adiposity, and endocrine and metabolic parameters in free-ranging rhesus macaques. 153 57

A blunted growth hormone (GH) response to several stimuli, including growth hormone-releasing hormone (GHRH), has been shown in obesity. Arginine (ARG) has been demonstrated to potentiate the GHRH-induced GH increase in normal subjects, likely acting via inhibition of hypothalamic somatostatin release. To shed further light onto the mechanisms underlying the blunted GH secretion in obesity, we studied the effect of ARG (0.5 g/kg infused intravenously [IV] over 30 minutes) on both basal and GHRH (1 micron/kg IV)-stimulated GH secretion. Eight obese subjects (aged 26.4 +/- 3.9 years; body mass index, 39.0 +/- 1.9 kg/m2) and eight normal control volunteers (aged 27.0 +/- 1.7 years; body mass index, 22.3 +/- 0.5 kg/m2) were studied. In obese subjects, the GH response to both GHRH and ARG was lower (P less than .01 and P less than .002, respectively) than in controls. ARG potentiated the GH response to GHRH in obese patients (P less than .0003). However, in these patients, the GH secretion elicited by GHRH, even when coadministered with ARG, persisted at reduced levels (P less than .005) when compared with controls. Basal insulin-like growth factor-1 (IGF-1) levels did not significantly differ in obese subjects and in normal subjects (161.1 +/- 37.0 v 181.0 +/- 12.8 micrograms/L). In conclusion, ARG enhances the blunted GHRH-induced GH increase in obese patients, but the GH responses to ARG alone and to ARG + GHRH persist at lower levels than in normals. Thus, our results suggest the existence of a reduced pituitary GH pool in obesity.
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PMID:Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity. 158 39

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. 170 70

Accelerated atherosclerosis accompanying diabetes mellitus, obesity, and some types of hypertension has been associated with hyperinsulinemia, augmented plasma plasminogen activator inhibitor type 1 (PAI-1), or both. We hypothesized that insulin and insulin-like growth factor type I (IGF-I) can influence synthesis of PAI-1, thereby potentially attenuating fibrinolysis. In HepG2 cells used as a model system, concentrations of insulin and IGF-I consistent with those seen in plasma independently stimulated PAI-1 synthesis. Accumulation of PAI-1 protein in conditioned medium over 24 hr was stimulated more with insulin alone than with the combination. Synergistic increases were evident, however, in the accumulation of PAI-1 protein over 48 hr with a concomitant increase in PAI-1 mRNA. A 10- to 20-fold increase in IGF binding protein I mRNA was seen 16-48 hr after exposure of the HepG2 cells to insulin and IGF-I, an increase abolished by cycloheximide. The results obtained are consistent with the hypothesis that hyperinsulinemia coupled with physiologic concentrations of IGF-I may attenuate fibrinolytic activity in vivo, thereby contributing to accelerated atherosclerosis.
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PMID:Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type I: implications for vascular disease in hyperinsulinemic states. 171 59

In this review article evidence is assembled from the neuroendocrinology of women with polycystic ovary-like syndrome (PCOS), to argue that the central dysregulation of gonadotropin secretion as found in the syndrome is not the cause of its development. The increased amplitude of luteinizing hormone (LH) pulses is explained by an increased pituitary sensitivity to gonadotropin releasing hormone (GnRH) due to prolonged unopposed estrogen exposure of the gonadotropic cells. The increase in pulse frequency cannot be used in the argument because it may be the cause for, as well the result of, the pathological status of the ovary. A good argument for a pathogenetic involvement of central factors, however, is the reversed day/night rhythm in adolescent girls with PCOS. A critical review of the literature does not give evidence of involvement of either obesity or catecholamines in the central abnormalities. Therefore they cannot cause PCOS via central feedback systems. The response of the gonadotropins to progesterone is the same as it is in normally cycling women. Androgens exert a variable effect on LH secretory patterns, although they do induce the typical change of PCOS in the ovaries. This argues for an ovarian rather than for a central cause. Endogenous opiates seem to be increased in PCOS. It can be argued that this should suppress both LH secretion and adrenal androgen secretion. It should also stimulate insulin-like growth factor (IGF)-binding proteins, thereby binding more IGF with less stimulatory action on the theca cells to produce androgens. Therefore endogenous opiates do not seem to be involved in the pathogenesis of PCOS either. Studies in PCOS during the recovery from GnRH agonist treatment show that the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is quite normal for some time during the recovery phase. However, PCOS always develops again. This therefore does not give a clue either. In pulsatile GnRH stimulation of PCOS patients, the LH and FSH secretory patterns completely normalize. However, the symptoms of PCOS continue under this stimulation and the clinical pattern does not change dramatically. This gives the best argument that PCOS is caused by one or more peripheral factors, which may be ovarian in origin, rather than by central factors.
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PMID:Neuroendocrine control in polycystic ovary-like syndrome. 179 49

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

The potential was examined for insulin, growth hormone and insulin-like growth factor (IGF-1) alone or in combinations to stimulate glycerophosphate dehydrogenase (GPDH) activity, a sensitive marker of differentiation of adipose precursor cells in primary culture. Insulin, but not growth hormone or IGF-1, stimulated GPDH in the presence of fetal calf serum and cat serum. The content of growth hormone in adult rat heparinised plasma seemed, however, important for such stimulation, but was also dependent on feeding status of the plasma donor, and was abolished by hypophysectomy of the cell donor. GPDH activity was then analysed in heparinised plasma in the over-night fasting state in humans to examine a potential influence of age, obesity and pregnancy. In comparison with non-obese adults, GPDH-stimulatory activity was higher in plasma from infants and small children. A similar trend was seen in plasma from teenagers. This activity was probably partly dependent on growth hormone, because this increase of activity could be inhibited by excess of anti-human growth hormone antiserum. Obesity in adulthood or among teenagers was not associated with any difference in plasma activity to stimulate cellular differentiation, and plasma from women during late pregnancy had a low stimulating capacity. Simultaneous analyses of the potential of plasma to stimulate lipid accumulation in adipose precursor cells was proportional to the triglyceride concentration. Overall, the inhibitory effect of antihuman growth hormone antiserum on the differentiating capacity of human plasma was small or non-existing. It is therefore suggested that in human plasma, factors other than growth hormone might be important for the differentiation of adipocyte precursor cells.
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PMID:Effects of age, obesity and growth-hormone on adipogenic activity in human plasma. 331 49

The absence of a distinct clinical syndrome calls for a strategy to reliably identify patients with hyposomatotropism. However, there is no consensus as to the most appropriate method of defining growth hormone (GH) deficiency in adults. Since GH secretion falls with senescence and is also reduced by obesity, both of these factors must be controlled for in such an evaluation. We have investigated the relative diagnostic merits of measuring (1) peak GH response to insulin-induced hypoglycemia (ITT), (2) mean 24-hour GH concentration derived from 20-minute sampling (IGHC), (3) serum IGF-I levels, and (4) serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) levels. These tests were undertaken in 23 patients considered GH-deficient from extensive organic pituitary disease and in 35-sex-matched normal subjects of similar age and body mass index. The ITT was the only test capable of distinguishing patients with organic GH deficiency from matched normal subjects. The sensitivity of the GH radioimmunoassay (0.2 ng/mL) limited the utility of IGHC measurements, since many subjects from both groups had undetectable values. Using a GH assay with a 100-fold greater sensitivity, we found a better but still incomplete separation of values between the two groups. There was a significant overlap of IGF-I and IGFBP-3 values, with only a third of GH-deficient subjects having low IGF-I values. The limitation of IGF-I has been confirmed by others, although its sensitivity as a diagnostic test is greater in young adults. We conclude that organic GH deficiency in adults can be reliably diagnosed by the ITT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defining growth hormone deficiency in adults. 747 18


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