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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this work was to study the effect of diabetes on 125I-labelled insulin-like growth factor (IGF) binding to specific serum binding proteins (IGFBPs) and the possible role of protein glycation in such an effect. Accordingly, ligand blotting and fructosamine assays were performed in serum samples from diabetic and non-diabetic eSS rats as well as in samples of normal rat serum previously incubated with different concentrations of glucose. IGFBPs with molecular weights of 24, 30 and 40 kDa were identified in samples from diabetic and non-diabetic rats. 125I-Labelled IGF-I binding to each of these fractions increased significantly in the serum of diabetic rats. IGF-I binding to IGFBP-40 increased significantly as a function of the degree of glycation of serum proteins. Conversely, the increased binding of IGFBP-24 and IGFBP-30 was related only to the glucose concentration attained at 120 min during the oral glucose tolerance test. Glycation of proteins of normal serum and the binding of labelled IGF-I increased as a function of glucose concentration in the incubation media. In these in-vitro glycated normal sera, only the binding to IGFBP-40 increased significantly; this increase was closely related to the amount of protein glycation. No clear and reproducible changes occurred with the binding of 125I-labelled IGF-I to IGFBP-24 and IGFBP-30 fractions. These results confirm the increase in the binding capacity of IGFBPs reported in diabetic animals. They also show that the increase in IGF-I binding to each IGFBP fraction is regulated by a different mechanism; whereas protein glycation induces changes in IGFBP-40, this mechanism does not affect the binding properties of the other two IGFBPs. The increased binding of IGFBP might affect the availability of free IGF-I, and the consequent alterations in IGF-I-dependent metabolic processes could explain the role of this growth factor in the pathogenesis of chronic complications of diabetes.
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PMID:Protein glycation: its role in the changes induced by diabetes in the properties of the serum insulin-like growth factor-I binding proteins. 172 Aug 5

The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.
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PMID:Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance. 195 1

We recently identified a 32 K mol wt insulin-like growth factor (IGF)-binding protein (BP) which is markedly increased in the serum of streptozotocin-diabetic rats and recognized by antiserum against the human amniotic fluid IGFBP (hIGFBP-1). In the present study we sought to confirm that this protein represents the rat homolog of IGFBP-1 (rIGFBP-1), and that rIGFBP-1 may, therefore, play an important role in the regulation of IGF bioactivity in experimental diabetes. Since the abundance of related hepatic mRNA is high in diabetic rats, we asked whether well differentiated H4EIIC3 rat hepatoma cells produce rIGFBP-1 and provide sufficient amounts of this protein for purification and further characterization. Specific IGF-binding activity in hepatoma conditioned medium was detected initially by incubation with 125I-labeled recombinant human IGF-II and precipitation with polyethylene glycol. Ligand blotting demonstrated a 32 K BP, identical in size to the major low mol wt IGFBP found in diabetic rat serum. Affinity labeling and immunoprecipitation confirmed that this BP is related to human IGFBP-1 and is distinct from the fetal rat IGFBP, rIGFBP-2. Incorporation of [35S]methionine into 32 K BPs confirmed synthesis by hepatoma cells. For purification of BPs, conditioned medium was collected in roller culture, and BPs were purified by ammonium sulfate precipitation, Sephadex G-75 chromatography, and reverse phase HPLC. Partial amino acid sequencing of purified protein demonstrated 68% identity with the human IGFBP-1 and distinguished this BP from previously characterized rat IGFBPs. Purified protein bound both IGF-I and IGF-II with high affinity. We conclude that the 32 K IGFBP produced by H4EIIC3 hepatoma cells in culture represents the rat form of IGFBP-1 (rIGFBP-1). Regulation of rIGFBP-1 may play an important role in the modulation of IGF bioactivity in experimental animals with metabolic disease. The availability of purified rIGFBP-1 and identification of a cell line that produces this BP will greatly facilitate future studies of IGFBP-1 in the rat model.
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PMID:Production of the rat type 1 insulin-like growth factor-binding protein by well differentiated H4EIIC3 hepatoma cells: identification, purification, and N-terminal amino acid analysis. 216 20

When insulin was administered to streptozotocin-induced diabetic female rats, the percentage of glycohemoglobin, growth rate, ovulatory cycle, uterus to body weight ratio, and insulin-like growth factor (IGF-I) level returned to near normal. In untreated diabetic rats there were no normal estrous cycles, and hepatic IGF-I mRNA (7.94 +/- 1.02 O.D. units per micrograms total RNA) levels were significantly lower than the control or insulin-treated groups in proestrus (16.47 +/- 0.91 and 17.15 +/- 1.84, respectively). Insulin therapy restored the hypothalamic-pituitary-ovarian axis with the reinstitution of normal estrous cycles. Plasma IGF-I levels were highest in non-diabetic proestrous animals (277 +/- 36.9 ng/ml), significantly higher than IGF-I levels in insulin-treated diabetic rats in diestrus (174 +/- 23.1 ng/ml), non-diabetic diestrus rats (165 +/- 18.4 ng/ml) and untreated diabetic rats (135 +/- 19.7 ng/ml). Plasma IGF-I levels were elevated in insulin-treated diabetic rats in proestrus (221 +/- 78.3 ng/ml), however this was not significantly different from any other group. The increases observed in plasma IGF-I and hepatic IGF-I mRNA after insulin therapy correlate with the normalization of sex hormone secretion. Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrus groups.
Diabetes Res Clin Pract 1990 Mar
PMID:The effect of ovarian function on insulin-like growth factor I plasma levels and hepatic IGF-I mRNA levels in diabetic rats treated with insulin. 218 62

Daily minocycline-treatment of streptozotocin-induced diabetic rats not only prevented a diabetes-caused atrophy of skin collagen mass (10-mos old rats), but also normalized skin collagen mass to match that of growing (ca. 1%/d) non-diabetic controls (4- and 5-mos old rats). The causative mechanism by which minocycline-treatment normalizes skin collagen mass must, in part, be related to a general anabolic effect on growth (body weight) because the effect on skin collagen mass correlates strongly to that on body weight. Consequently, a minocycline-stimulated increase of a systemic factor (such as insulin-like growth factor) is not unlikely. The anabolic effect of minocycline-treatment of diabetic rats is also expressed as a normalized cellular ribosome mass (an index of total protein synthetic capacity) and a normalized absolute rate of collagen production. (Calculation of an absolute rate was justified by an apparent maximum saturation of the prolyl-tRNA pool(s) of skin, maximum saturation obtained by the pool-flooding approach). The normalized skin ribosome amount does not, however, explain a selective effect of minocycline-treatment on collagen production as opposed to that for non-collagen protein, this selective effect measured as relative collagen production. To explain such selectivity, the inhibition of diabetes-induced excess skin collagenase activity seems unlikely. (This inference is based on results from a preliminary study indicating that recently [less than 2 h] synthesized collagen is not degraded by the excess collagenase in skin of diabetic rats). Thus, the principal collagen fraction acted on by pathologically excess collagenase might be collagen at a later stage (greater than 2 h after synthesis) in its life cycle. (Another possibility for the selective effect of minocycline on collagen production, as yet untested, is reduced intracellular procollagen degradation.) Overall, this is the first study aimed at discerning the mechanism(s) by which minocycline-treatment enhances the rate of collagen production in tissues of a diabetic rat. For future studies, the extent to which the positive effect on growth, ribosome mass, and rate of collagen production contributes to the change of collagen mass must, along with the known minocycline-inhibition of collagenase activity, be quantified. Such quantification is a prerequisite for evaluating the chemotherapeutic efficacy of minocycline-treatment on collagen-degradative diseases.
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PMID:Minocycline-treatment of diabetic rats normalizes skin collagen production and mass: possible causative mechanisms. 237 16

Insulin is a potent mitogen for many cell types in vitro. During tissue culture, supraphysiological concentrations of insulin are necessary to promote cell replication in connective or musculoskeletal tissues. Insulin promotes the growth of these cells by binding, with low affinity, to the type I insulin-like growth factor (IGF) receptor, not through the high affinity insulin receptor. In other cell types, such as hepatocytes, embryonal carcinoma cells, or mammary tumor cells, the type I IGF receptor is virtually absent, and insulin stimulates the growth of these cells at physiological concentrations by binding to the high affinity insulin receptor. Both receptor systems activate phosphorylation reactions within the cell which extend to ribosomal proteins. Insulin acts synergistically with other factors, such as platelet-derived growth factor and epidermal growth factor, to stimulate the progression of cells through the cycle of proliferation. Abnormal insulin secretion or action, before or after birth, often is associated with disordered growth suggesting that insulin may function as a growth factor in vivo. Poor growth follows impaired insulin secretion in diabetes mellitus. This is associated with reduced circulating levels of IGF's which may be partly responsible for the growth failure. Insulin has a direct action on release of IGF's from the liver in vitro, but during experimental diabetes there is a reduced number of hepatic somatotropic receptors which could limit the ability of growth hormone to regulate IGF release. Diabetic children, treated conventionally, have normal circulating IGF levels, but both growth rate and serum IGF concentration may increase dramatically when diabetic control is optimized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin as a growth factor. 241 20

The serum levels of the low molecular form of insulin-like growth factor binding protein (IGFBP) was determined in 56 outpatients with diabetes mellitus by a radioimmunoassay developed for amniotic 35 kDa IGFBP. The mean level of 35 kDa IGFBP was found to be threefold higher in insulin dependent diabetes mellitus (IDDM), 112 +/- 13 ng/ml, than in age matched controls, 37 +/- 2 ng/ml, while the mean level in non-insulin dependent diabetes mellitus (NIDDM), 16 +/- 2 ng/ml, was decreased. In hospitalized IDDM patients there was a significant correlation (r = 0.91, p less than 0.01) between fasting blood-glucose and 35 kDa IGFBP levels, not found in NIDDM patients. During insulin infusion the 35 kDa IGFBP levels declined with a half-life of 60-120 min. The decline in IGFBP continued even after the establishment of steady state B-glucose at 4.7 mmol/l. In conclusion, the elevated 35 kDa IGFBP levels in IDDM can be attributed to insulin deficiency and may reflect a reduced bioavailability of the IGFs at the target cells.
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PMID:Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus. 246 6

Evidence is accumulating that a non-GH dependent insulin-like growth factor-binding protein (IGF-BP) is not only a carrier protein but also has an active role in the growth process. We have measured levels of this IGF-BP, using a specific RIA, over 12 or 24-h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normal the IGF-BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 micrograms/l. The levels of IGF-BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 micrograms/l if a long-acting insulin preparation was administered in the evening but were 400-500 micrograms/l if the long-acting preparation was administered in the morning. The IGF-BP was strongly correlated with plasma glucose in this latter group. In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF-BP and free insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circadian variation of GH-independent IGF-binding protein in diabetes mellitus and its relationship to insulin. A new role for insulin? 247 66

Circulating insulin-like growth factor binding protein (IGF BP) activity is increased in animals with streptozotocin-induced diabetes. Separation of BPs by SDS/PAGE for ligand and immunoblot analysis revealed that a 32,000 molecular weight BP is present and increased in diabetic serum. This BP is immunologically distinct from the low molecular weight fetal rat BP (rBP2) and is related to the human amniotic fluid BP (hBP1) that is increased in patients with insulin dependent diabetes mellitus.
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PMID:Identification of a type 1 insulin-like growth factor binding protein (IGF BP) in serum from rats with diabetes mellitus. 247 84

Insulin-like growth factor II is secreted primarily by the liver and is reported to be transcribed in many primary hepatocellular carcinoma (PHC) cell lines. We have studied diagnostic significance of serum IGF-II in chronic liver diseases using specific enzyme immunoassay. Serum IGF-II levels (mean +/- SE) were decreased in chronic hepatitis (538 +/- 51 ng/ml; N = 29), liver cirrhosis (427 +/- 45; 50) and PHC (260 +/- 41; 17) compared to controls (830 +/- 49; 57). Serum IGF-II was not different from controls in any of nonhepatic diseases such as diabetes (1032 +/- 97; 19) pancreatic cancer (1413 +/- 282; 8), chronic pancreatitis (999 +/- 126; 17), peptic ulcer (1186 +/- 43; 11), irritable bowel syndrome (1002 +/- 109; 12), gastrointestinal tract cancer (1250 +/- 216; 21) and chronic renal failure (733 +/- 135; 14). In liver diseases serum IGF-II showed a significant correlation with liver function test (negative with retention of indocyanine green and total bile acids; positive with albumin, thrombo-test, and cholinesterase). These results suggest that serum IGF-II reflects a reduced production of IGF-II in the liver and that it can be an index for the residual capacity of liver function.
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PMID:Serum insulin-like growth factor II in chronic liver disease. 253 15


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