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Query: UMLS:C0011849 (diabetes)
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We evaluated the relationship of insulin-like growth factor (IGF)-I to incidence and progression of diabetic retinopathy over a 6-year interval in a large population-based study of diabetes in southern Wisconsin. Participants included people with younger-onset diabetes (n = 66 adolescents, n = 661 adults > or = 18 years of age) and older-onset diabetes (n = 285 for those using insulin, n = 248 for those not using insulin). Fundus photographs were graded in a masked fashion using standardized protocols to determine the severity of retinopathy in each eye. Serum IGF-I levels were measured during 1984-1986 using a double-antibody radioimmunoassay. Mean IGF-I was highest in adolescents (499.1 micrograms/l), lower in younger-onset adult (280.1 micrograms/l), and lowest in the older-onset group (205.7 and 221.2 micrograms/l for older-onset group using insulin and not using insulin, respectively). The incidence of retinopathy was not significantly higher in people with higher IGF-I levels in any group. The odds of developing diabetic retinopathy in 6 years for each 10 micrograms/l increase in IGF-I after controlling for age, glycosylated hemoglobin, and duration of diabetes at baseline was 1.21 (95% confidence interval [CI] 0.95-1.54) for adolescents; 1.00 (95% CI 0.93-1.08) for younger-onset adults; 0.93 (95% CI 0.85-1.02) for the older-onset group using insulin; and 0.99 (95% CI 0.95-1.04) for the older-onset group not using insulin. In summary, IGF-I was not associated with 6-year incidence or progression of diabetic retinopathy in any of the groups.
Diabetes 1995 Feb
PMID:Does insulin-like growth factor I predict incidence and progression of diabetic retinopathy? 785 35

The insulin-like growth factor system, which includes the IGFs, IGF-binding proteins and IGF receptors, plays an essential role in normal growth and development, as well as the cellular differentiation of a number of other important systems, including the reproductive and immune systems. IGF action has also been implicated in several pathological conditions, including tissue repair, malnutrition, diabetes and malignancy.
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PMID:Insulin-like growth factors and their receptors in normal physiology and pathological states. 792 Sep 91

Rabson-Mendenhall syndrome was initially reported in 1956 by Rabson et al., who described three children with familial hyperplasia of pineal gland and diabetes mellitus. Characteristic features of this syndrome are low birthweight, thickened nails, hirsutism, acanthosis nigricans, dental precosity and dysplasia, polycystic ovary, abdominal proturbance, phallic enlargement and insulin resistant diabetes mellitus. Most patients die of ketoacidosis and intercurrent infection associating with extreme insulin resistance during mid-childhood. This syndrome appears to show autosomal recessive inheritance. Recent reports provide evidence that mutations in the insulin-receptor gene are, at least in pant, the cause of this syndrome, and that recombinant IGF-I (insulin-like growth factor-1) reduces hyperglycemia in patients of this syndrome.
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PMID:[Rabson-Mendenhall syndrome]. 798 91

Fetal mesenchyme-derived factors are likely to play an important role in pancreatic islet development and growth. We have used primary cultures of human fetal pancreatic tissue to identify growth factors that have morphogenic, mitogenic, and insulinotropic activity. The formation of islet-like cell clusters (ICCs) during a 6-day culture was stimulated two- to threefold by hepatocyte growth factor/scatter factor (HGF/SF) basic fibroblast growth factor (FGF)-2, and to a lesser extent by keratinocyte growth factor (FGF-7) and insulin-like growth factor-II (IGF-II). In contrast, transforming growth factor-beta (TGF-beta) had a strong inhibitory effect. The ICCs formed during HGF/SF stimulation consisted mainly of epithelial cells, whereas FGF-2-induced ICCs were predominantly nonepithelial. Furthermore, although both FGF-2 and HGF/SF increased the total insulin content of the cultures, only HGF/SF increased the insulin content per DNA. Quantitatively, HGF/SF stimulated a 2.3-fold increase in the proportion of insulin-positive cells and a 3-fold higher number of replicating beta-cells. Blocking of the IGF-I receptor inhibited ICC formation but did not affect their insulin content. Immunoneutralizing TGF-beta resulted in increased cell growth and insulin content, indicating the presence of an endogenous inhibitory TGF-beta activity in the model system. Our results suggest that HGF/SF may be an important component of the fetal mesenchyme-derived factors responsible for pancreatic islet development. HGF/SF also may prove valuable for supporting the in vitro growth of islet cells.
Diabetes 1994 Jul
PMID:Hepatocyte growth factor/scatter factor has insulinotropic activity in human fetal pancreatic cells. 801 61

Glomerular hypertrophy is reported in several endocrine disorders such as acromegaly and diabetes mellitus, where abnormalities of growth hormone and insulin-like growth factor (IGF-I) have been reported. In the present report, we have cultured bovine and human glomerular endothelial cells, and bovine glomerular epithelial and mesangial cells, and characterized the expression of IGF-I mRNA and its receptor in these cells. High affinity, specific receptors for IGF-I were identified in all three types of cells by radioreceptor assays. Receptor number (Ro) derived by Scatchard analysis revealed an unusually high number of Type I IGF receptors, approx. 1.2 x 10(5) receptors/cell in glomerular endothelial cells. Affinity crosslinking studies and immunoprecipitation with antibodies against the Type I IGF receptor identified the alpha-subunit of the IGF-I receptor as having a molecular mass of 140 kDa. Biologically, IGF-I was more potent than insulin or IGF-II in stimulating DNA synthesis in glomerular endothelial cells. Northern blot analysis showed that glomerular and aortic endothelial cells expressed IGF-1 mRNA of 1.7 kb. In contrast, renal glomeruli showed several IGF-1 mRNAs of 7.5, 1.7 and 1.2 kb. Thus, the demonstration of both a prepondence of Type I IGF receptors coupled with the growth promoting effects of IGF-I in glomerular endothelial and epithelial cells, as well as the local production of IGF-I mRNA suggests that IGF-I serves an important role as an autocrine or paracrine regulator of the growth of renal glomeruli.
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PMID:Characterization of type I IGF receptor and IGF-I mRNA expression in cultured human and bovine glomerular cells. 826 20

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.
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PMID:Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion. 834 58

This study evaluated the insulin and insulin-like growth factor-1 (IGF-1) receptor function among patients with type II diabetes who did or did not respond to 1 month of treatment with the oral sulfonylurea agent glyburide. Patients with type II diabetes were initially placed on dietary treatment alone. Patients whose fasting plasma glucose level exceeded 9 mmol/L were enrolled in a prospective 1-month trial of oral glyburide. Clinical, laboratory, and receptor characteristics were assessed before and after glyburide therapy and were compared between the responders and non-responders as well as with matched nondiabetic control subjects. Of the 34 patients who participated in the study, 17 (50%) responded (fasting plasma glucose decreased to 7.8 mmol/L or by 30% from basal level) to the drug. There were no clinical parameters that could distinguish between patients responding and not responding to glyburide. Iodine 125-labeled insulin binding to intact erythrocytes tended to be higher among responders both before and after glyburide. However, the studies of specific insulin binding and insulin receptor tyrosine kinase activities of purified erythrocyte receptors could not distinguish between the two groups of patients with diabetes either before or after glyburide treatment. Compared with weight-matched nondiabetic controls, the erythrocyte insulin receptor tyrosine kinase activity in the patients with diabetes was significantly (by about 45%) decreased. Studies of the IGF-1 receptor likewise did not reveal differences between the two diabetic groups. In conclusion, one half of ambulatory patients with type II diabetes showed a satisfactory hypoglycemic response to a short-term glyburide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin and IGF1 receptor function among type II diabetic responders and nonresponders to glyburide. 845 33

Serum levels of insulin-like growth factor I are reduced in patients with Type 1 (insulin-dependent) diabetes mellitus. To evaluate the role of the hepatic growth hormone receptor in the decreased serum concentrations of insulin-like growth factor I, serum levels of the high affinity growth hormone-binding protein, which is qualitatively and quantitatively related to the hepatic growth hormone receptor, and of insulin-like growth factor I were measured in 70 children and adolescents with Type 1 diabetes and 105 healthy control children. Analysis of variance revealed a significant negative effect of Type 1 diabetes on serum levels of the growth hormone-binding protein and of insulin-like growth factor I. In the diabetic patients, serum levels of the growth hormone-binding protein were positively related to body mass index and to insulin dose per kg body weight, and were not influenced by pubertal stage, gender, or plasma levels of haemoglobin A1c. Serum levels of insulin-like growth factor I increased during early puberty reaching peak levels at mid-puberty and decreasing thereafter. No relationship was found between serum levels of growth hormone-binding protein and of insulin-like growth factor I. Our data suggest that decreased liver somatogenic receptor levels, as reflected by the concentrations of circulating growth hormone-binding protein, play a minor role in the suppressed concentrations of circulating insulin-like growth factor I. Post-growth hormone receptor defects or changes in the insulin-like growth factor binding proteins probably contribute more to the lower serum levels of insulin-like growth factor I.
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PMID:Serum levels of growth hormone-binding protein and insulin-like growth factor I in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. 846 73

An immunoradiometric assay (IRMA) for the measurement of insulin-like growth factor-II (IGF-II) in human plasma has been developed, optimized and evaluated clinically in normal subjects and patients with disorders of the GH/IGF-I axis. Six monoclonal antibodies (MAbs) to recombinant human IGF-II (rhIGF-II) were produced, all of which had low cross-reactivity with rhIGF-I (< 0.01%) and insulin (< 0.01%). Compatibility of pairs of MAbs was tested in two-site IRMAs using three radioiodinated MAbs and three MAbs linked to Sephacryl S-300 (with separation of bound and free radiolabelled MAb by sucrose layering). Seven pairs of MAbs bound rhIGF-II and the combination of 125I-labelled W3D9 and W2H1 linked to solid phase was selected. The optimized assay had a completion time of 4 h, a minimum detection limit of 30 ng/ml (2.5 standard deviations from the zero standard) and detected a single peak of endogenous IGF-II in normal plasma which co-eluted with rhIGF-II after acid gel chromatography. IGF-II was measured in formic acid/acetone extracts of plasma from 16 normal subjects (mean 685, range 516-1008 micrograms/l), four acromegalic patients (mean 637, range 553-700 micrograms/l), fourteen patients with type-1 diabetes (mean 635, range 247-753 micrograms/l), nine patients with uraemia (mean 423, range 78-850 micrograms/l), and three patients with Laron-type GH insensitivity (75, 35 and 36 micrograms/l). No significant fluctuations were detected between samples obtained hourly from 08.00 to 19.00 h in normal subjects. Low levels of IGF-binding proteins (IGFBPs) remaining in plasma extracts may interfere with the measurement of IGF-II and give rise to falsely elevated IGF-II levels in radioimmunoassays or falsely suppressed levels in IRMAs. Such interference did not occur with the IRMA when used to measure IGF-II in extracts from normal subjects, acromegalic patients and patients with type-1 diabetes, and the addition of excess rhIGF-I in order to displace IGF-II from residual IGFBPs had no effect on IGF-II measurements in these samples. However, levels of IGF-II measured in extracts from patients with Laron-type GH insensitivity and patients with uraemia increased markedly after preincubation with excess rhIGF-I. The accurate measurement of IGF-II by IRMA in extracts from these subjects therefore requires the displacement of IGF-II from IGFBPs prior to assay. We conclude that, in contrast to radioimmunoassays, the two-site IRMA developed here provides a practical, rapid and specific method for the measurement of IGF-II in human plasma.
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PMID:Measurement of insulin-like growth factor-II in human plasma using a specific monoclonal antibody-based two-site immunoradiometric assay. 849 71

Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and prolactin (PRL) in blood and urine were observed in 20 patients with acromegaly in a double-blind placebo-controlled 14-day clinical trial with the somatostatin analog octreotide. Hormones were determined by the same radioimmunoassays in blood and urine. Significant reduction of GH and IGF-1 during octreotide treatment compared to placebo was seen in blood but not in urine. Patients with diabetes mellitus, 2 of the 20 patients, showed notably increased urinary GH and IGF-1 in relation to blood levels. Therefore, results without the two diabetic patients were calculated, showing significant reduction of urinary GH and IGF-I during treatment on some, but not all observation days. The intraindividual variations of GH and IGF-1 were greater in urine than in blood. PRL levels were not significantly affected by octreotide either with or without the two diabetic patients. In conclusion, this study indicates, that GH and IGF-1 in blood are preferable to urinary GH and IGF-1 as response markers during treatment of acromegaly with octreotide. One disadvantage with urinary assessments of GH and IGF-1 in acromegaly seems to be the relatively higher excretion in patients with diabetes mellitus.
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PMID:Growth hormone and insulin-like growth factor-1 in blood and urine as response markers during treatment of acromegaly with octreotide: a double-blind placebo-controlled study. 851 80


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