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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The migration of retinal pigment epithelial (RPE) cells from their normal anatomic position to a new position in the vitreous cavity is a critical feature of proliferative vitreous retinopathy. To determine if insulin-like growth factor I (IGF I), which is present in the vitreous fluid of diabetics, stimulates RPE cells, we examined the effects of IGF I on the proliferation, chemotaxis, and release of plasminogen activator by these cells. At the concentrations of IGF I tested, significant proliferation of RPE cells is seen. Significant chemotaxis of the RPE cells also is seen at all the concentrations of IGF I tested. The mean number of migrating cells per high-powered field in control studies was 43 +/- 13 (x +/- SEM), and for IGF I at 2.5 ng and 50 ng/ml the mean numbers of migrating cells were 96 +/- 17 and 483 +/- 62, respectively (P less than 0.001 for each comparison). The IGF I response was noted to be dose-dependent. The chemotactic response noted at 50 ng/ml of IGF I was greater than the positive chemotactic control of 10% fetal calf serum. Addition of alpha IR-3, an IGF I receptor antibody, eliminated the IGF I chemotactic response. The effect of IGF I on the secretion of plasminogen activators was assessed using an immunological assay for tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Media conditioned by RPE cells have measureable levels of PAI and t-PA antigen. IGF I supplementation resulted in an increase of t-PA secretion and PAI secretion over basal levels. These studies support a role for IGF I in modulating RPE cell function.
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PMID:Insulin-like growth factor I stimulates proliferation, migration, and plasminogen activator release by human retinal pigment epithelial cells. 211 Dec 35

It has recently been demonstrated that immunoassayable kidney insulin-like growth factor I concentration increases 24-48 h after induction of diabetes, preceding the initial renal hypertrophy. To elucidate whether this increase is due to increased local production we studied rat kidney insulin-like growth factor I gene expression during the first four days after induction of streptozotocin diabetes. Eighteen hours after injection with streptozotocin the diabetic animals were divided into two groups, one of which was treated with insulin, and daily for four days animals from each group were taken out for investigation. After four days the wet kidney weight had increased from baseline by 20% (from 687 +/- 23 to 827 +/- 6 mg (mean +/- SEM), p less than 0.01) in the untreated diabetic group, while no significant increase occurred in the insulin-treated group (687 +/- 23 vs 732 +/- 21 mg, NS). Kidney insulin-like growth factor I increased rapidly from baseline, the rise amounting to 52% after 48 h (from 271 +/- 11 to 411 +/- 32 ng/g, p less than 0.01) with a decline to control level on day four in the untreated diabetic group. Kidney insulin-like growth factor I remained unchanged in the insulin-treated diabetic group. Insulin-like growth factor I mRNA was measured by solution-hybridization assay. No differences were found in kidney insulin-like growth factor I mRNA between the two diabetic groups over the study period, while in liver, insulin-like growth factor I mRNA tended to be lower on day four in diabetic rats when compared to insulin-treated rats (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. 219 79

Recombinant human insulin-like growth factor I (IGF-I) was administered subcutaneously to each of 5 normal human subjects at doses of 0 mg/kg (control), 0.06 mg/kg, or 0.12 mg/kg successively at one week intervals. After 0.06 mg/kg or 0.12 mg/kg IGF-I injections, plasma IGF-I levels increased from 185 +/- 17 ng/ml (mean +/- SEM) to maximal levels of 396 +/- 21 ng/ml at 3 hours and from 169 +/- 14 ng/ml to 480 +/- 27 ng/ml at 4 hours, respectively. These two peak values were statistically different (p less than 0.05). After 0.06 mg/kg and 0.12 mg/kg IGF-I administration, blood glucose levels decreased from 85 +/- 2 mg/dl to minimal levels of 73 +/- 3 mg/dl at 3 hours and from 83 +/- 1 mg/dl to 50 +/- 4 mg/dl at 2 hours, respectively. These two minimal values were statistically different (p less than 0.001). Serum insulin and C-peptide levels were decreased in a dose dependent manner after IGF-I administration. There were no changes between blood urea nitrogen levels before and 4 hours after IGF-I administration. The urinary GH concentration decreased after 0.06 mg/kg IGF-I administration, but increased and maintained normal values after 0.12 mg/kg IGF-I administration.
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PMID:Effects of sc administration of recombinant human insulin-like growth factor I (IGF-I) on normal human subjects. 222 47

Poorly controlled diabetes mellitus in humans and animals is often accompanied by impaired growth. We undertook this study in young rats to determine whether the reduction in growth rate associated with streptozotocin (STZ)-induced diabetes might be related to changes in both serum insulin-like growth factor I (IGF-I) and IGF-II levels, and, if so, whether these changes reflect alterations in serum growth hormone (GH) and in hepatic IGF-I and IGF-II gene expression. Serum rat GH (rGH) levels were variable during the first 4 days after STZ administration, but during the subsequent 5- to 11-day period the mean (+/- SEM) levels in insulin-treated (DI) (21.4 +/- 4.9 ng/mL) and untreated (D) (8.5 +/- 1.5 ng/ml) diabetic rats were significantly (P less than .001) lower than in controls (C) (117.8 +/- 22.9 ng/mL). Multiple transcripts of IGF-I (7.0, 4.0, 1.9, 1.0 kb), but barely detectable amounts of IGF-II mRNA, were found in the livers of normal and diabetic rats by Northern blot analysis. Using dot blot analysis, we have shown that the abundance of total hepatic IGF-I mRNA in untreated, growth-retarded diabetic animals decreases rapidly over a period of 3 days after STZ administration. Both serum IGF-I and IGF-II levels are also diminished during this interval in these markedly hyperglycemic rats. Insulin treatment for 3 to 4 days, started either immediately (6 hours) or within 3 days after administering STZ, blunts diabetes-induced impairment of growth and restores mean hepatic IGF-I mRNA abundance to control levels, but does not normalize serum IGF-I and IGF-II concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of streptozotocin-induced diabetes mellitus on growth and hepatic insulin-like growth factor I gene expression in the rat. 240 28

Previous in vivo studies have suggested a long-term regulatory role for insulin in the exocrine pancreas. To directly study the long-term effects of insulin on the pancreas in vitro, we have used cultured AR42J cells, a rat cell line that is derived from a transplantable tumor of the acinar pancreas. Hormone-binding experiments with 125I-labeled hormones indicated that AR42J cells have insulin receptors, relatively fewer receptors for insulin-like growth factor II (IGF-II), and no detectable receptors for insulin-like growth factor I (IGF-I). Insulin at concentrations as low as 1 nM stimulated the growth of these cells, as measured by an increase in DNA and protein content, and in cell number. At 100 nM, where insulin had a maximal effect, the growth of AR42J cells was stimulated by 46.1 +/- 10.9% (mean +/- SEM, N = 11). Insulin increased the amylase activity of AR42J cells over the same concentration range that it stimulated growth; at 100 nM, insulin increased amylase by 91.0 +/- 15.4% (mean +/- SEM, N = 23). Immunoprecipitation of [35S]methionine-labeled proteins revealed that insulin induced a selective increase of amylase synthesis over general protein synthesis. These studies indicate, therefore, that insulin stimulates both growth and amylase synthesis of AR42J cells.
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PMID:Insulin, via its own receptor, regulates growth and amylase synthesis in pancreatic acinar AR42J cells. 241 17

The binding of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) to cell membranes was determined in 14 renal cancers and in 13 normal kidney tissues adjacent to the tumors. The soluble 34K IGF binding protein (34K IGF-BP) content and the phosphotyrosyl-protein phosphatase activity in renal cancer tissue and adjacent normal tissue were also determined. The specific EGF receptor binding in renal cancers was 12.7 +/- 2.5% (mean +/- SEM) as compared to 2.6 +/- 0.2% (mean +/- SEM) in normal tissues (p less than 0.01). Phosphotyrosyl-protein phosphatase activity in renal cancer tissue was less than half of that observed in normal renal tissue (p less than 0.01). The highest IGF-I binding was observed in 5 renal cancers although no consistent differences between IGF-I binding to tumor and normal tissues were observed. Both EGF and IGF binding to kidney tissue were higher than binding to gastro-intestinal tissue irrespective of whether normal or malignant tissues were compared. All normal kidney tissues and 7 of 8 kidney tumors contained measurable amounts of 34K IGF-BP as determined by RIA and the cross-linking technique. In 2 tumor tissue samples the 34K IGF-BP content was increased 8- and 15-fold over that seen in adjacent normal kidney tissue, whereas in the 6 other renal cancers the 34K IGF-BP was similar to that observed in normal kidney tissue.
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PMID:Binding of epidermal growth factor and insulin-like growth-factor I in renal carcinoma and adjacent normal kidney tissue. 254 41

We have investigated whether the previously demonstrated stimulatory actions of growth hormone on DNA synthesis and (pro)insulin biosynthesis and release of isolated adult rat islets of Langerhans are mediated by an autocrine release of somatomedin-C/insulin-like growth factor I (SM-C/IGF I). In medium containing 1% fetal calf serum, the presence of 16.7 mmol/l glucose, or 2.7 mmol/l glucose supplemented with a concentrate of essential amino acids, caused a significant increase in 3H-thymidine incorporation and insulin release compared to 2.7 mmol/l glucose alone but no increase in SM-C/IGF I release. Further supplementation with 1 microgram/ml growth hormone increased 3H-thymidine incorporation and SM-C/IGF I release within all groups, and insulin release in the 16.7 mmol/l glucose and 2.7 mmol/l plus amino acid groups. The ability of growth hormone to increase 3H-thymidine incorporation in the presence of 16.7 mmol/l glucose, but not its action on insulin release, was partly inhibited by a monoclonal antibody against SM-C/IGF I (control cultures 100%; growth hormone alone 261 +/- 27%, mean +/- SEM; growth hormone + anti-SM-C/IGF I 179 +/- 21%; p less than 0.05, n = 18). Growth hormone, but not 100 ng/ml SM-C/IGF I, increased insulin biosynthesis assessed as immunoprecipitable 3H-labelled insulin by 45%, but this was accompanied by a similar increase in overall protein synthesis. Similarly growth hormone, but not SM-C/IGF I caused a 75% increase in glucose oxidation by islets. Both growth hormone and SM-C/IGF I failed to increase the cellular uptake of alpha-aminoisobutyric acid or 3-O-methyl glucose over a 90 min period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone regulation of DNA replication, but not insulin production, is partly mediated by somatomedin-C/insulin-like growth factor I in isolated pancreatic islets from adult rats. 266 10

Growth hormone is reported to increase renal plasma flow (RPF) and glomerular filtration rate (GFR) in some but not all studies. The discrepant results could be due to a delay in the effects of growth hormone on renal function. We therefore examined whether a growth hormone injection does increase RPF and GFR, whether this increase is delayed, and whether elevation in RPF and GFR is associated with increased plasma levels of insulin-like growth factor I (IGF-I). Seven normal adults received a single intramuscular injection of growth hormone, 0.15 mg/kg, and serial PAH and inulin clearances were then monitored for three consecutive days. Plasma growth hormone levels peaked an average of 2.25 hours after injection, at 128 +/- 12 SEM ng/ml, and then began to decrease; on the second day values were only slightly elevated and on the third day they were not different from baseline. Plasma IGF-I, analyzed by direct radioimmunoassay, did not change on the first day during 5.5 hours of measurements after injection. By the second day, plasma IGF-I was elevated to over twice baseline levels (P less than 0.05) and remained elevated on the third day (P less than 0.05). RPF and GFR did not change from baseline (546 +/- 19 and 100 +/- 3 ml/min/1.73 m2, respectively) during the 5.5 hours after injection on the first day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The delayed effect of growth hormone on renal function in humans. 270 79

To define further the alterations in growth hormone (GH) secretion that occur in childhood hypothyroidism, we quantified spontaneous nocturnal secretion in seven patients with primary hypothyroidism. We examined the relationship between plasma insulin-like growth factor I (IGF-I) and GH secretory profile in each patient before and during therapy with L-thyroxine. In contrast to the results of previous studies that used pharmacologic tests of GH release, spontaneous GH secretion was consistently attenuated in the hypothyroid state. Mean nocturnal GH levels were reduced by 58% (1.48 +/- 0.38 ng/ml, mean +/- SEM) in comparison with values obtained during L-thyroxine therapy (3.54 +/- 0.71 ng/ml, p less than 0.01). Coincident with the reduced levels of GH, plasma IGF-I concentrations were lower in patients before therapy (0.46 +/- 0.20 U/ml) compared with concentrations during therapy (1.50 +/- 0.34 U/ml, p less than 0.01). In treated, euthyroid patients, GH and IGF-I levels were equivalent to those of normal children. The excellent correlation (r = 0.77) between plasma IGF-I and mean nocturnal GH concentrations indicates that reduced plasma IGF-I levels in hypothyroidism probably result from suppressed GH secretion.
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PMID:Attenuation of spontaneous, nocturnal growth hormone secretion in children with hypothyroidism and its correlation with plasma insulin-like growth factor I concentrations. 272 11

Insulin may mediate the hyperandrogenism that frequently occurs in patients with insulin-resistant states. To test this hypothesis, we studied five normal women and one woman with hyperandrogenism, insulin resistance, and acanthosis nigricans with the hyperinsulinemic-euglycemic clamp technique. Each woman received a 0.1 U/kg insulin bolus dose, followed by a 10 mU/kg X min insulin infusion for 12-16 h. In the normal women, an average insulin level of 1832 +/- 292 (+/- SEM) microU/ml was achieved; serum glucose was clamped at 116 +/- 5 mg/dl. At this level, insulin may bind to the insulin-like growth factor I receptor as well as to its own receptor. Contrary to our working hypothesis, a rise in serum testosterone did not occur in any women during insulin infusion, and in one women, serum testosterone levels decreased. When analyzed as a percentage of the basal value, serum progesterone levels fell 20% in the normal women within the first 2 h of insulin infusion, but did not change thereafter. Dehydroepiandrosterone sulfate (DHEA-S) levels, however, uniformly and progressively decreased by 39% after 12 h of insulin infusion in the normal women and by 31% at 14 h in the woman with hyperandrogenism, insulin resistance, and acanthosis nigricans. The fall in serum DHEA-S levels was not due to diurnal rhythmicity, as the changes in serum DHEA-S levels did not correlated with those in serum cortisol. Suppression of PRL release also was excluded as a cause of the fall in DHEA-S levels. These results indicate that acute hyperinsulinemia of 12- to 16-h duration does not increase serum testosterone or DHEA-S concentrations and, indeed, can cause a decline in serum DHEA-S levels in both normal women and the single woman studied with hyperandrogenism, insulin resistance, and acanthosis nigricans.
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PMID:The effects of hyperinsulinemia on serum testosterone, progesterone, dehydroepiandrosterone sulfate, and cortisol levels in normal women and in a woman with hyperandrogenism, insulin resistance, and acanthosis nigricans. 294 16


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