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)

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

Prepubertal gilts of control (n = 30), obese (n = 30), or lean (n = 29) genetic lines were implanted with no, one, or two implants of porcine somatotropin (pST, each delivers 2 mg/d) for 6 wk starting at 160 d of age to determine whether pST affects ovarian function. At 4 mg/d, pST increased (P < .01) numbers of 4.0- to 6.9-mm (medium) follicles but not (P > .10) numbers of 1.0- to 3.9-mm (small) follicles per gilt. Both doses of pST increased (P < .01) serum and follicular fluid (FFL) concentrations of IGF-I and activity of IGF binding protein (IGFBP)-3 and 36-kDa IGFBP in all three lines; IGFBP-3 was the predominant IGFBP. In comparison, binding activity of IGFBP-2 was decreased (P < .01) in serum by 4 mg of pST but increased (P < .05) in FFL by 4 mg of pST. Lean gilts had lower (P < .05) serum concentrations of IGF-I and less (P < .05) total binding activity of IGFBP than control and obese gilts. Concentrations of estradiol in FFL of small and medium follicles tended (P < .08) to be increased by 2 mg/d of pST, whereas FFL concentrations of progesterone were unaffected by pST. Obese and control gilts had twofold greater (P < .05) FFL progesterone concentrations than lean gilts. We conclude that sustained-release implants of pST can stimulate follicular growth, increase concentrations of IGF-I in serum and FFL, and increase IGFBP activity in serum of genetically divergent lines of gilts without an adverse effect on ovarian function.
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PMID:Administration of porcine somatotropin by a sustained-release implant: effect on follicular growth, concentrations of steroids and insulin-like growth factor I, and insulin-like growth factor binding protein activity in follicular fluid of control, lean, and obese gilts. 752 95

We studied the gene expression of the insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and growth hormone (GH) receptor (GHR)/GH binding protein (GHBP) in liver of rats treated neonatally with monosodium glutamate (MSG). The MSG-treated rats showed severe growth retardation and obesity compared to saline-injected controls. Serum IGF-I levels in MSG-treated rats were significantly lower than in the controls after 6 weeks of age (p < 0.01). IGF-I gene expression increased with age and was significantly lower in MSG-treated rats than in the controls (p < 0.01). IGFBP-3 gene expression was unaffected by age in both MSG-treated male rats and the controls, but was less in MSG-treated female rats than in their controls between 6 to 8 weeks of age. In our study of GHR/GHBP gene expression, MSG-treated rats of both sexes displayed a distinct 1.5 kbase band encoding GHBP RNA. We speculated that these changes reflect disruption of GH secretion in in vivo experimental models. Thus, MSG-treated rats are useful as in vivo models for study of the effect of GH disruption on developmental gene expression.
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PMID:Studies of gene expression in liver of insulin-like growth factor (IGF)-I, IGF binding protein-3 and growth hormone (GH) receptor/GH binding protein in rats treated neonatally with monosodium glutamate. 753 19

A major problem of weight reduction in obesity is the undesirable loss of lean body mass that accompanies fat loss, particularly in severe calorie restriction. In order to achieve maximal fat loss, but without great loss of lean tissue, growth hormone (GH) in a dose of 6 U/day subcutaneously was added to a very low calorie diet and an exercise program for moderately obese subjects. Body weight, body composition and hormonal status were studied during an eight-week period. The results of seven patients using GH (seven females; mean age 39.1 +/- 7.9 years; mean body weight 94.2 +/- 10.7 kg; mean body mass index 35.1 +/- 2.3 kg/m2) were compared to the results of eight patients using placebo (two males, six females; mean age 38.9 +/- 10.4 years; 100.0 +/- 11.0 kg; mean body mass index 32.9 +/- 1.9 kg/m2). The groups were comparable for demographic data. Both serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) levels became significantly higher in the GH group (p = 0.001 and p = 0.014, respectively). Mean serum IGF-I levels increased from 29.0 +/- 8.19 nmol/l at randomization to 50.14 +/- 14.66 nmol/l after 2 weeks in the GH group, whereas the levels decreased from 34.25 +/- 10.26 nmol/l to 27.63 +/- 8.14 nmol/l in the placebo group. After two weeks, IGF-I and IGFBP-3 levels stabilized. In the first half of the study serum free triiodothyronine (T3) levels remained stable in the GH group, whereas a decrease was found in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone administration in addition to a very low calorie diet and an exercise program in obese subjects. 753 3

In order to determine which factors influence the large variations in sensitivity to gonadotrophins witnessed in women with polycystic ovary syndrome (PCOS), a prospective study was conducted of the correlation between basal clinical and endocrinological features and gonadotrophin requirements of 20 women with clomiphene-resistant PCOS undergoing ovulation induction. Baseline evaluation of serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, fasting insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) were performed before administering gonadotrophin-releasing hormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin (HMG) was given in a standard individualized protocol according to ovarian response, until human chorionic gonadotrophin (HCG) was given. Serum concentrations of insulin, IGF-1, and IGFBP-1 were unaffected by GnRHa. The BMI correlated positively with insulin and inversely with IGFBP-1 serum concentrations and insulin and IGFBP-1 were inversely correlated. The amount of HMG required correlated positively with BMI and insulin concentrations and inversely with IGFBP-1 in the whole group and these correlations were maintained in the sub-group of lean women. No correlation was observed between HMG requirements and IGF-1 or other hormones. Women with hyperinsulinaemia and low IGFBP-1 concentrations required significantly more HMG. Multiple regression analysis revealed that insulin concentration is the most significant determinant of HMG requirement even when dissociated from BMI. We concluded that requirements of HMG in PCOS is not merely determined by obesity but by a cardinal role of insulin concentrations which, when high, induce, hypothetically, a hyperandrogenic intrafollicular milieu.
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PMID:Serum levels of insulin-like growth factor-1, IGF binding protein-1 and insulin and the response to human menopausal gonadotrophins in women with polycystic ovary syndrome. 867 13

Numerous endocrine abnormalities of the growth hormone (GH)-insulin-like growth factor axis have been described in patients with both anorexia nervosa and obesity during childhood and adolescence. These alterations include changes in the levels of 24-hour spontaneous GH secretion, high-affinity, low-capacity GH binding protein (GHBP), IGF-I, IGF-II and the IGF binding proteins (IGFBPs). However, the existing information is sometimes confusing and contradictory. Furthermore, little or no data in these pathologies are available concerning IGFBP-2 or free IGF-I. We have analysed the GH-IGF axis in large populations of adolescents with anorexia nervosa and prepubertal children with exogenous obesity. These patients were studied at the time of diagnosis and at two timepoints during nutritional therapy and normal weight recovery. The results of these studies using age- and sex-matched controls are described here.
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PMID:Disturbances in the growth hormone-insulin-like growth factor axis in children and adolescents with different eating disorders. 935 Apr 40

In 1988, insulin-like growth factor-binding protein-1 (IGFBP-1) became the first characterized member of a group of structurally related soluble proteins which specifically bind and modulate the actions of the IGFs. Since then, a wealth of information has accumulated regarding the physiology of this dynamic serum protein. In this review, we update our 1993 summary (Lee PDK et al. Proc Soc Exp Biol Med 204:4-29) of the status of IGFBP-1 research. The IGFBP-1 protein sequence contains 12 N-terminal and 6 C-terminal cysteine residues which are conserved in other mammalian IGFBP-1 sequences and amongst other IGFBPs; both of the cysteine-rich regions are required for optimal IGF binding. The nonconserved IGFBP-1 midregion may act as both a hinge which defines ligand binding characteristics and as a specific target for protease activity. Integrin-binding and phosphorylation sites within the IGFBP-1 sequence have functional significance in vitro, but their physiologic relevance in vivo have not been defined. The human IGFBP-1 and IGFBP-3 genes are contiguous and located in close proximity to the homeobox A (HOXA) gene cluster on chromosome 7. The other IGFBP genes, located on chromosomes 2, 12, and 17, are also associated with HOX clusters, suggesting evolutionary linkage of the IGFBP and HOX gene families. Similarities between the hIGFBP-1 and phosphoenolpyruvate kinase (PEPCK) promoters, including regions conferring insulin, glucocorticoid, and cyclic adenosine-monophosphate responses, are consistent with our previous hypothesis that IGFBP-1 is involved in regulation of glucose metabolism. The tissue-specific patterns of IGFBP-1 gene expression in liver, kidney, decidua, and ovary may be due to stimulation of IGFBP-1 transcription by hepatic nuclear factor 1 (HNF1) proteins. Clinical and basic studies of IGFBP-1 physiology have been aided by several recently developed assay methods. Numerous investigations have confirmed that insulin, via inhibition of IGFBP-1 transcription, is the primary determinant of IGFBP-1 expression both in vitro and in vivo. IGF-I and IGF-II also have specific inhibitory effects on IGFBP-1 expression. Glucocorticoids and cAMP stimulate IGFBP-1 transcription, but these effects are observed only in conditions of low or absent insulin effect. Other stimulants of IGFBP-1 expression include thyroid hormones and epidermal growth factor. Phorbol ester stimulation of IGFBP-1 expression can supersede the effects of insulin in vitro;however, the mechanism and in vivo correlates of this effect have not been determined. Cytokines and, perhaps, growth hormones may affect IGFBP-1 expression, perhaps by altering the regulatory actions of insulin; this effect may have important clinical relevance. IGFBP-1 expression is upregulated in liver and (nonhuman) kidney during postinjury regeneration. The IGF-inhibitory actions of IGFBP-1 has been confirmed by numerous in vitro studies and several in vivo animal investigations, including administration of recombinant IGFBP-1 and IGFBP-1 transgenic models. IGFBP-1 has been shown to inhibit somatic linear growth, weight gain, tissue growth, and glucose metabolism. Moreover, IGFBP-1 appears to be a primary determinant of free IGF-I levels in serum. Excess levels of IGFBP-1 may contribute to growth failure in intrauterine growth restriction and in pediatric chronic renal failure, while low IGFBP-1 levels are associated with obesity and with cardiovascular risk factors in insulin resistance syndromes. Serum IGFBP-1 measurements may be useful biochemical marker in these pathologic conditions. IGFBP-1 is expressed in decidualized stromal cells of the uterine endometrium and in ovarian granulosa cells. IGFBP-1, together with IGFs, insulin, ovarian steroids, cytokines, and other factors, is involved in a complex system which regulates menstrual cycles, ovulation, decidualization, blastocyst implantation, and fetal growth. (ABSTRACT TRUNCATED)
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PMID:Insulin-like growth factor binding protein-1: recent findings and new directions. 940 39

We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 microg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRH-driven pulsatile GH secretion (in randomly ordered sessions) were quantitated by deconvolution analysis of 24-h (10-min sampling) serum GH concentration profiles measured in an ultrasensitive (threshold 0.005 microg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 +/- 0.1 basal vs 2.4 +/- 0.4 microg/l treatment; P = 0.0001), total daily pulsatile GH production rate (21 +/- 9.5 vs 97 +/- 17 microg/l/day; P = 0.01), GH secretory burst frequency (11 +/- 0.5 vs 17 +/- 0.3 events/day; P = <0.01), and mass of GH released per burst (1.1 +/- 0.4 vs 5.9 1 microg/l; P < 0.01), as well as serum IGF-I (261 +/- 33 vs 436 +/- 37 microg/l; P = 0.005), insulin (45 +/- 13 vs 79 +/- 17 mU/l; P = 0.0002), and IGF binding protein (IGFBP)-3 (3320 +/- 107 vs 4320 +/- 114 microg/l; P = 0.001) concentrations, while decreasing IGFBP-1 levels (16 +/- 1.2 vs 14 +/- 0.09 microg/l; P = 0.02). Serum total testosterone and estradiol concentrations did not change. GHRH treatment also reduced the half-duration of GH secretory bursts, and increased the GH half-life. GHRH-stimulated 24-h serum GH concentrations and the mass of GH secreted per burst were correlated negatively with age (R[value]:P[value] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P = -0.80:0.0001 and -0.65:0.0005 respectively), but positively with serum testosterone concentrations (R:P = +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated plasma IGF-I increments correlated negatively with age and body mass index, and positively with serum testosterone, but not with percentage body fat. Cosinor analysis disclosed persistent nyctohemeral rhythmicity of GH secretory burst mass (with significantly increased 24-h amplitude and mesor values) but unchanged acrophase during fixed pulsatile GHRH infusions, which suggests that both GHRH- and non-GHRH-dependent mechanisms can modulate the magnitude (but only non-GHRH mechanisms can modulate the timing) of somatotrope secretory activity differentially over a 24-h period. In summary, diminished GHRH action and/or non-GHRH-dependent mechanisms (e.g. somatostatin excess, putative endogenous growth hormone-releasing peptide deficiency etc.) probably underlie the hyposomatotropism of aging, (relative) obesity, and/or hypoandrogenemia. Preserved or increased tissue IGF-I responses to GHRH-stimulated GH secretion (albeit absolutely reduced, suggesting GHRH insensitivity in obesity) may distinguish the pathophysiology of adiposity-associated hyposomatotropism from that of healthy aging.
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PMID:Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men. 970 80

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.
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PMID:Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children. 986 79

We reported a boy with panhypopituitarism after removal of a suprasellar teratoma and pituitary stalk transection at the age of 3 months. His growth was accelerated after 5 years of age without growth hormone (GH) therapy, although he had poor height growth until age 4 under treatment with hydrocortisone, levothyroxine sodium, and desamino-D-arginine vasopressin (DDAVP). Hyperphagia and obesity developed after surgery. Endocrinological examination revealed no GH response to glucagon, low serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3). Serum prolactin was normal, but serum insulin was high. Some patients who received an operation for craniopharyngioma were reported to achieve normal growth without GH secretion, but the mechanism is still unknown. High serum levels of prolactin or insulin can be associated with normal IGF in GH deficient patients. This patient had obesity and high serum insulin, which may be related to growth without GH secretion.
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PMID:A boy with normal growth in spite of growth hormone deficiency after resection of a suprasellar teratoma. 1089 Jan 95


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