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

The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax1) was lower in obesity than in AN or control. The low-affinity constants (Ka2) were similar in the three groups, and its binding capacity (Bmax2) was similar in the AN patients and the controls, but significantly lower in the obese. [125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. 131 1

The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergistic GH secretagogues, once daily for 60 consecutive days. Although pituitary weights and GH concentrations were higher in obese rats administered the peptides than in obese rats administered saline, stimulated GH secretion was lower in obese rats than in lean rats. However, compared to those in lean rats, plasma insulin-like growth factor-I and insulin concentrations were higher in the obese rats regardless of treatment. The GH secretagogues did not alter food intake or body weight gain in sexually mature obese rats, whereas body weight gain was significantly increased when they were administered to prepubertal obese rats. Although glucose tolerance was impaired in both groups of obese rats, it improved in obese rats administered GHRH and GHRP-6 compared to that in obese rats administered saline. On the other hand, plasma cholesterol concentrations were elevated in obese rats administered the GH secretagogues but not saline. In conclusion, the results of this study suggest that hyposensitivity to GHRH and GHRP-6 in obese Zucker rats results from high concentrations of plasma insulin-like growth factor-I that negatively feedback on stimulated GH secretion. Nonetheless, daily episodes of endogenous GH secretion resulting from chronic coadministration of GH secretagogues significantly influenced the pituitary gland as well as lipid and carbohydrate metabolism.
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PMID:Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats. 144 17

Obesity is associated with normal or increased growth despite diminished GH secretion compared to lean children. The mechanism by which adequate growth is maintained in the presence of low GH levels is unknown, but is possibly mediated at the GH receptor level. To probe this hypothesis, we examined the relationship between GH responsivity, body mass index (BMI) and plasma GH-binding protein (GH-BP)/receptor level in 43 GH-deficient children during treatment with a fixed dose of GH (0.18 mg/kg.week). Before treatment, BMI [expressed as standard deviation score (SDS) for age (BMI-SDS)] did not correlate with either growth velocity or serum insulin-like growth factor-I (IGF-I). In contrast, after 12 months of GH therapy BMI-SDS correlated directly with plasma IGF-I (P < 10(-5)) and growth velocity (P < 10(-3)). These findings parallel those obtained for GH-BP vs. the response to GH, suggesting that BMI and GH-BP are covariants. The interrelationships among BMI, GH-BP, and response to GH were further probed by multiple regression analysis. Partial correlation coefficients vs. response to GH were consistently stronger for GH-BP than for BMI-SDS, indicating that GH-BP is the dominant factor between these two covariants in determining responsiveness to GH. The data suggest a primary role for GH-BP/receptor levels in determining GH action, with secondary but significant effects of nutrition and degree of adiposity. The latter may be mediated through the impact of nutrition and body mass on GH-BP/receptor levels.
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PMID:The role of body mass in the response to growth hormone therapy. 146 49

In order to evaluate the GH/insulin-like growth factor-I (IGF-I) axis in the polycystic ovary syndrome (PCO), 21 women aged 18-38 yr were studied. The GH responses to the GH-releasing hormone (GHRH), and plasma concentrations of IGF-I were measured in seven obese women with PCO, seven obese healthy controls without PCO, and in seven nonobese subjects. Total GH secretion, as expressed by the integrated GH response to GHRH, in PCO obese women (617.4 +/- 150 micrograms/L.min) and in obese women without PCO (327.1 +/- 161.4 micrograms/L.min) were lower than that in nonobese healthy controls (3181.4 +/- 644.3 micrograms/L.min, P less than 0.001 and P less than 0.001, respectively). Plasma concentrations of IGF-I in obese PCO women (199.5 +/- 39.1 micrograms/L), and in obese women without PCO (192.4 +/- 36.8 micrograms/L) were similar to the IGF-I levels in nonobese controls (224.3 +/- 33.2 micrograms/L). In obese women with and without PCO, a negative correlation was found between the body mass index and the peak GH responses to GHRH (r = -0.639, P less than 0.02) and between age and IGF-I levels (r = -0.520, P less than 0.05). These findings suggest that an abnormality of the GH/IGF-I axis in PCO women may be due to coexistent obesity.
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PMID:An abnormality of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovary syndrome due to coexistent obesity. 153 30

Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia.
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PMID:Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion. 160 98

Plasma insulin-like growth factor-I (IGF-I) concentrations and the effects of exogenous IGF-I administration were determined in 26 rhesus monkeys; each animal was well characterized regarding its degree of obesity, plasma glucose and insulin levels, and glucose tolerance (KG). Five separate groups were identified: lean normal, obese normoinsulinemic and normoglycemic, obese hyperinsulinemic with normal glucose tolerance, impaired glucose tolerant, and spontaneously diabetic (type II, non-insulin-dependent diabetes mellitus [NIDDM]). Basal plasma IGF-I levels in all monkeys ranged from 249 to 1,093 ng/mL and were strongly associated with age (r = -.66; P less than .001) and KG (r = .59; P less than .001), but not with body weight, body fat, or fasting plasma glucose or insulin levels. In addition, the acute insulin-like effects of exogenously administered IGF-I on glucose disappearance were studied in vivo in a dose-response comparison to insulin (subcutaneous administration of IGF-I at doses of 50, 100, or 200 micrograms/kg v insulin at 0.3 U/kg). Five hyperinsulinemic normoglycemic monkeys (fasting plasma glucose, 67 +/- 2 mg/dL; insulin, 163 +/- 42 microU/mL) and overt type II diabetic monkeys (fasting plasma glucose, 201 +/- 13 mg/dL; insulin, 38 +/- 6 microU/mL) each underwent a series of three to five experiments to determine the time course and degree of hypoglycemia induced by IGF-I as compared with insulin or with control (saline) injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factor-I in non-insulin-dependent diabetic monkeys: basal plasma concentrations and metabolic effects of exogenously administered biosynthetic hormone. 194 41

Aging is associated with both a relative accumulation of body fat and a reduction in growth hormone (GH) secretion. This study was devised to investigate the relationship between plasma insulin-like growth factor-I (IGF-I), an index of GH secretion, and anthropometric indices of body fat in normal subjects of various ages. Somatic and biochemical indices of nutrition were assessed in 107 subjects between the ages of 17 and 83 years who attended an outpatient clinic for general health supervision. Plasma IGF-I correlated negatively with age in both males (r = -.44, P = .001) and females (r = -.40, P = .005). In addition, plasma IGF-I correlated negatively with body mass index (BMI) (r = .35, P = .006), percentage of standard triceps skinfold (TSF) (r = -.26, P = .05), and percentage of standard weight (r = -.35, P = .006) in males, but not in females. Multiple regression analysis indicated that in males, BMI and percentage of standard weight correlated with plasma IGF-I independent of the effect of age. We conclude that adiposity and aging are independently associated with decreased plasma IGF-I concentrations. The negative correlations between indices of adiposity and IGF-I were observed only in males, whereas the age-associated decline in IGF-I was present in both males and females. We speculate that sex differences in the gonadal steroid milieu, combined with declining GH secretion in both sexes, may contribute to the age-associated development of obesity in males.
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PMID:The relationship between insulin-like growth factor-I, adiposity, and aging. 235 77

It is well established that spontaneous and stimulated growth hormone (GH) secretion is diminished in human obesity. In contrast to classic GH deficiency, obesity is not associated with hypopituitary levels of circulating total (extractable) insulin-like growth factor-I (IGF-I) and reduced somatic growth. Thus, the riddle of "normal growth without GH" in obese children and the mechanisms behind the GH suppression have remained unsolved. Insulin reduces hepatic production of IGF-binding protein-1 (IGFBP-1), an in vitro inhibitor of IGF bioactivity, and it has been suggested that the obesity-related hyperinsulinemia may increase free (bioactive) IGF in vivo by reducing the concentration of IGFBP-1. We have recently developed a method that during near in vivo conditions isolates the free, unbound fractions of IGF-I and IGF-II in human serum. Using this method, we have determined overnight fasting serum levels of free IGFs in obese subjects and compared the results with levels of total (extractable) IGFs, IGFBPs, GH, and insulin. The study included 92 healthy subjects (56 males and 36 females) allocated to three age-matched groups depending on body mass index (BMI): 31 controls (BMI < or = 25), 33 subjects with moderate obesity (25 < BMI < 30), and 28 subjects with severe obesity (BMI > or = 30). Fasting serum insulin correlated positively (r = .61, P < .0001) with BMI and was significantly elevated in moderate and severe obesity (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free insulin-like growth factors in human obesity. 747 10

The genetically obese Zucker rat is a widely used model of early-onset obesity. Like obese children, these obese rats are hyperinsulinemic and have low GH secretion. However, data on linear growth and insulin-like growth factor-I (IGF-I) levels in this model are scanty and contradictory. In the present study, we investigated linear growth and its hormonal control in Zucker rats (male and female) from 4-20 weeks of age. In the obese animals, compared to their lean littermates, the naso-anal length was normal or slightly greater, whereas the tails and femurs were shorter. The plasma concentration of IGF-I increased between 4-20 weeks of age, and IGF-I levels were normal or slightly higher in the obese animals. The serum level of IGF-binding protein-3 (IGFBP-3) measured by Western ligand blotting was not significantly different in lean vs. obese rats. To assess the IGF-I response to GH, bovine GH was administered (250 micrograms/100 g BW, ip, daily for 3 days) to 16- to 20-week-old female Zucker rats; plasma IGF-I concentrations increased more in the obese (percent increase over baseline, 347 +/- 44% vs. 194 +/- 31%; P < 0.01). These results show that despite low GH secretion, genetically obese Zucker rats have 1) normal linear (nasoanal) growth, 2) normal or increased circulating levels of IGF-I and IGFBP-3, and 3) increased plasma IGF-I responses to exogenous GH. These results suggest that the GH-independent growth in this model could result from direct effects of hyperinsulinism on circulating IGF-I and IGFBP-3 levels and/or indirect effects through increased GH receptor function.
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PMID:Hormonal control of growth in the genetically obese Zucker rat. I. Linear growth, plasma insulin-like growth factor-I (IGF-I) and IGF-binding proteins. 750 40

Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal IGFBP-1 levels and a decrease in basal insulin levels occurred in the normal controls, whereas no such changes were observed in the obese subjects. After caloric restriction 24-hr GH release, IGFBP-1 levels and insulin levels were similar in control subjects and obese subjects after weight loss. This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat and perpetuate the obese state.
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PMID:Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity. 753 71


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