Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein lipase (LPL) hydrolyzes lipoprotein triglyceride into nonesterified fatty acids, which are then reesterified and stored in adipose tissue. Previous studies have demonstrated increases in LPL in response to insulin-like growth factor I and GH when added in vitro. This study examined the effects of acromegaly treatment on adipose tissue LPL. Ten patients with clinically active acromegaly were recruited. A fasting adipose tissue biopsy was performed both before and 3 months after treatment with octreotide (8 patients) or surgery plus octreotide (2 patients). With treatment, mean baseline insulin-like growth factor I levels fell from 6.41 to 3.98 U/mL (normal, < 2.2 U/mL; P < 0.05), and serum glycohemoglobin fell from 8.6 to 7.2 (normal, < 6.8). Adipose LPL was measured in the heparin-released fraction as well as the cellular fraction extracted with nonionic detergent (EXT). After treatment of acromegaly, there was no change in heparin-released fraction LPL activity or immunoreactive mass. However, there was an increase in EXT activity from 0.73 +/- 0.33 to 1.83 +/- 0.58 nEq/min.10(6) cells (mean +/- SEM; P < 0.05) and an increase in EXT mass from 4.1 +/- 0.89 to 11.4 +/- 2.0 ng/10(6) cells (P < 0.05). There was no change in LPL messenger ribonucleic acid levels with treatment, determined using both quantitative polymerase chain reaction and Northern blotting. Thus, treatment of acromegaly resulted in an increase in the intracellular level of the LPL protein, with no change in messenger ribonucleic acid levels, suggesting posttranscriptional regulation of LPL. These changes in LPL may be due to improved insulin sensitivity, or to other changes associated with acromegaly treatment.
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PMID:Effects of acromegaly treatment and growth hormone on adipose tissue lipoprotein lipase. 759 31

1. Insulin-like growth factor I is a major mediator of growth-promoting activities. We studied the ventricular insulin-like growth factor I gene expression at mRNA and peptide levels in 24 heart transplant recipients (14 children and 10 adults), using 'slot blot' hybridization with insulin-like growth factor I cDNA probe and a specific radioimmunoassay. 2. Ventricular insulin-like growth factor I mRNA was detected in all the cardiac transplant children but was below the limit of detection in the cardiac transplant adults. Ventricular insulin-like growth factor I levels were significantly higher in the transplant children [174 +/- 15 (SEM; range 39-950) pg/mg soluble protein] than in transplant adults [39 +/- 2 (range 14-85) pg/mg soluble protein, P < 0.01, n = 14]. Circulating levels of insulin-like growth factor I in the cardiac transplant children [164 +/- 10 (range 105-192) ng/ml] and adults [176 +/- 15 (range 126-244) ng/ml] were within normal ranges for children and adults. 3. These results suggest that the human heart is a site for insulin-like growth factor I production and provide support for an autocrine role for insulin-like growth factor I in the ventricle, despite cardiac denervation.
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PMID:Ventricular expression and circulating levels of insulin-like growth factor I in heart transplant recipients. 767 68

This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21-62 years) with persistent growth hormone (GH) elevation (duration 1-15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 micrograms three times daily. The dose then was reduced to 200 micrograms three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0 +/- 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Four years' treatment of resistant acromegaly with octreotide. 771 80

We have previously shown that an episode of resistance exercise provokes an acute rise in circulating growth hormone (GH), and that this rise is severely blunted in older men and women. To determine whether this impairment simply reflects the decreased physical fitness of older people, we studied the effects of long-term resistance training on circulating levels of GH and insulin-like growth factor I (IGF-I) and on the acute GH response to exercise in 5 men and 9 women, aged 69.6 +/- 1.1 yrs (SEM). Subjects were randomly assigned to either an exercise program, consisting of 12 weight-lifting exercises (3 sets of 8 repetitions, 3 times each week) or to a control group. After testing maximum baseline strength by the 1 RM method, subjects returned to the laboratory for assessment of basal GH and IGF-I levels and the GH response to exercise. Venous blood was drawn at baseline, after each of 12 exercises (3 sets of 8 repetitions at 85% 1 RM), and every 2 minutes into the first 10 minutes of recovery. The exercise circuit with blood sampling was repeated at 15, 30 and 52 weeks for both groups. Basal GH and IGF-I values did not change in either group throughout the training period nor did the GH secretory response to exercise. Three exercisers had a peak GH concentration greater than 8 micrograms/l after 30 weeks of training, although only one of these showed a significant increase (29 micrograms/l) after 52 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a sustained program of resistance training on the acute growth hormone response to resistance exercise in older adults. 795 9

Development of preovulatory follicles was studied during the oestrous cycle in two experiments designed to examine the effects of short-term lack of insulin on preovulatory follicular function and (Expt 2 only) ovulation. In Expt 1, on day 12 of the third postpubertal oestrous cycle, insulin treatment was discontinued in streptozocin-induced diabetic gilts (n = 4), and on day 18, ovaries were removed from the diabetic gilts and from four normal untreated gilts. Diabetic gilts had a higher percentage of macroscopically atretic follicles (29.4 versus 6.8%; SEM = 5.9, P < 0.03) than did normal gilts. Binding of 125I-labelled hCG by freshly collected granulosa cells from non-atretic follicles was similar in diabetic and normal gilts. Diabetic gilts had more LH peaks in 3 h on days 12-17 of the oestrous cycle than did normal gilts (2.3 versus 1.6; SEM = 0.12; P < 0.01). Serum oestradiol and progesterone concentrations were not affected by treatment, but serum testosterone was increased (P < 0.01) in diabetic gilts. In Expt 2, insulin treatment was withdrawn from nine diabetic gilts on day 12 of the oestrous cycle and ten normal gilts served as controls. On day 18, ovaries were removed from six diabetic and six normal gilts; four normal and three diabetic gilts were ovariectomized 25 days after oestrus. Follicular diameter of diabetic gilts tended to be smaller than that of control (control: 3.95 versus diabetic: 3.01 mm; SEM = 0.4, P < 0.08) and the proportion of follicles with histologic evidence of atresia was higher in diabetic gilts (control: 29 versus diabetic: 47%; SEM = 5; P < 0.05) on day 18. In both experiments, the insulin-like growth factor I (IGF-I) and oestradiol concentrations of follicular fluid of diabetic gilts untreated with insulin from day 12 to day 18 was lower than in nondiabetic gilts. After day 18 in Expt 2, normal gilts exhibited oestrus (duration of cycle was 20 +/- 0.5 days) accompanied by preovulatory surges in oestradiol and LH, whereas diabetic gilts did not exhibit oestrus or ovulate. In diabetic gilts, oestradiol concentrations were lower compared with those of normal gilts, and LH patterns were characterized by two (two gilts) or three (one gilt) increases of more than 2 ng ml-1 between day 18 and day 25. Thus, impaired follicular function in diabetic gilts is not explained by decreased function of the hypothalamo-pituitary axis, since LH was not decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of diabetes mellitus during the luteal phase of the oestrous cycle on preovulatory follicular function, ovulation and gonadotrophins in gilts. 806 95

In a series of acromegalic patients the effects of CV 205-502, a new long-acting dopamine-agonist drug, on growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were evaluated in an open study. After acute administration of CV 205-502 (0.0375 mg, po) in 12 patients. GH levels did not change, whereas PRL values significantly decreased and remained suppressed for 24 h. In the 14 patients who underwent chronic CV 205-502 treatment (at daily doses of 0.150-0.600 mg/day given at bedtime or b.i.d. for up to 12 months). GH and IGF-I levels fell significantly from 60 +/- 17 (mean +/- SEM) micrograms/l to 28 +/- 10 micrograms/l and from 1127 +/- 84 micrograms/l to 738 +/- 57 micrograms/l, respectively (p < 0.05). A retrospective comparison with the results obtained for the same patients during a previous chronic bromocriptine treatment (at daily doses of 5-20 mg given t.i.d. or q.i.d.) did not show any significant difference in the suppression of GH levels between the two treatments; no bromocriptine-resistant patient was CV 205-502 sensitive, even at the highest CV 205-502 dose used. We conclude that in acromegaly chronic treatment with this new dopaminergic drug has a GH- and PRL-lowering effect that is similar to but more prolonged than that of bromocriptine, and normal or near-normal GH and IGF-I levels may be obtained in a few patients with b.i.d. administration. However, no GH-lowering effect is observed in bromocriptine-resistant patients.
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PMID:CV 205-502 in acromegaly. 810 Mar 75

The objective of this study was to determine the presence, regulation, and localization of specific receptors for insulin-like growth factor I (IGF-I) in primate reproductive tissues. Uteri were obtained from baboons either during the menstrual cycle, after ovariectomy with or without steroid treatments, or during early pregnancy (Days 18-60 postovulation [PO]). Placental and decidual tissues were collected from baboons during late pregnancy (Days 130-160). Localization of type I IGF receptor was determined by indirect immunocytochemistry (alpha IR3 antibody), and levels of type I IGF receptors were determined by affinity cross-linking and binding assays. Specific staining for type I IGF receptors was present in the membranes of glandular epithelial cells throughout the cycle and early pregnancy; however, there was a decrease in staining intensity by the late luteal phase and also throughout early pregnancy compared to the late follicular phase. Specific receptor staining was absent in stromal cells throughout the cycle. By Day 19 PO, stromal cells directly under the trophoblast were positive for type I IGF receptor, and an increase in stromal staining at the implantation site was observed as pregnancy proceeded. Stromal staining was apparent in non-implantation site tissue by Day 32 PO. Some placental villi showed positive receptor staining as early as on Day 18 PO, and an increase in the number of positive villi was apparent as pregnancy progressed. An 125I-IGF-I-protein complex of approximately 140,000 daltons, corresponding to the alpha subunit of the type I IGF receptor, was detected in endometrial, placental, and decidual membranes. The intensity of this signal was high in endometrium from the follicular phase, whereas low levels were detected in endometrium from the luteal phase. Throughout early pregnancy, alpha receptor subunit was present in placental and decidual membranes; alpha receptor subunit increased in placenta as pregnancy proceeded. An additional 125I-IGF-I-protein complex of 43,000 daltons, corresponding to IGF binding protein-1 (IGFBP-1), was present in decidual membranes and appeared to increase as pregnancy proceeded. Specific binding of 125I-IGF-I to placental membranes was displaced by unlabeled IGF-I and alpha IR3 antibody, whereas both unlabeled IGF-I and IGF-II competed equally for binding to decidual membranes. Scatchard analysis of 125I-IGF-I binding to placental membranes revealed a single class of high-affinity receptors (KD = 2.35 +/- 0.8 nM; mean +/- SEM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization, localization, and regulation of receptors for insulin-like growth factor I in the baboon uterus during the cycle and pregnancy. 819 60

We studied catch-up growth following withdrawal of glucocorticoid administration in seven intact prepubertal cynomolgus monkeys. To reduce stress during blood sampling, a vascular access port was implanted subcutaneously in each animal for the duration of the study. After a baseline observation period of 50 weeks, the monkeys received injections of dexamethasone at a dose of 100 micrograms.kg-1.day-1 for 15 weeks. Growth velocity was monitored every 3 weeks by measuring lower leg length and body weight. Spontaneous serum growth hormone (GH) concentrations and GH levels after insulin and L-dopa stimulation, as well as serum insulin-like growth factor I (IGF-I) and plasma thyrotropin, triiodothyronine and thyroxine, were measured during the study. Differences between animals were analyzed by repeated measures analysis of variance and Student's paired t-test. Mean +/- SEM growth velocity (mm/3 weeks) decreased from 0.90 +/- 0.08 during the baseline period to 0.29 +/- 0.07 (p < 0.001) during the period of growth retardation, and increased to 1.23 +/- 0.2 (p < 0.001) during the period of catch-up growth. Spontaneous GH and peak GH levels following insulin did not show any significant variation during the study. Peak GH during the L-dopa test decreased from 15.4 +/- 3.2 micrograms/l during the baseline period to 6.2 +/- 2.4 micrograms/l during the period of growth retardation (p < 0.05), and increased to 23.0 +/- 5.9 micrograms/l during the period of catch-up growth (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine profile of catch-up growth in the cynomolgus monkey. 823 58

Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s.c. dose of recombinant insulin-like growth factor I (40 micrograms/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1 +/- 28.2 ng/ml, mean +/- SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; p = 0.01), as were the insulin requirements for euglycaemia (0.25 +/- 0.02 compared with 0.31 +/- 0.04 mU.kg-1.min-1; p = 0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9 +/- 2.7 compared with 67.9 +/- 16.0 mU/l; p = 0.001) but no significant differences in ketone or lactate levels were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with type 1 (insulin-dependent) diabetes mellitus. 835 87

Acute and chronic studies in rats have shown that administration of human recombinant insulin-like growth factor I (rhIGF-I) lowers renal vascular resistance and increases RPF, GFR and proximal tubular phosphate absorption. In the present study we examined the effects of subcutaneous injections of rhIGF-I on glomerular and tubular function in eight normal men. Individuals were studied for 5.5 consecutive days in a clinical research center while they ate a constant diet. Four subjects were studied in a non-volume expanded state (Group 1) and four individuals were evaluated during a saline load. From the second to the fourth day, subjects received subcutaneous injections of rhIGF-I, 60 micrograms/kg, at 0800, 1400 and 2000 hours. After commencing the rhIGF-I injections, serum IGF-I levels rose quickly and remained at about three to four times that of baseline throughout the period of rhIGF-I injections. In both the normal and the saline loaded subjects, renal vascular resistance decreased and RPF and GFR (PAH and inulin clearances) rose quickly and were clearly altered within six hours after starting the rhIGF-I injections. RPF had increased by 32 +/- 3% and 33 +/- 2% (grand mean +/- SEM) in the normal and the saline loaded subjects, and GFR rose by 22 +/- 3% and 36 +/- 4% in the two groups. In both groups the absolute and the fractional excretion of phosphate decreased markedly during rhIGF-I treatment, but the absolute and fractional excretion of calcium did not change. The urinary fractional and absolute excretion of albumin and IgG also increased, although slightly, with rhIGF-I injections. There was no consistent effect of IGF-I on tubular sodium handling. These findings demonstrate that in normal men subcutaneous injections of rhIGF-I greatly increase RPF, GFR, and tubular phosphorus reabsorption and enhances microproteinuria.
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PMID:Effects of insulin-like growth factor I on renal function in normal men. 844 Dec 34


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