Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus

Brismar, Kerstin; Gutniak, M.; Pòvoa, Guilhèrme; Werner, Sigbritt; Hall, Kerstin

doi:10.1007/bf03350189

Cited by 160 publications

(77 citation statements)

References 15 publications

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“…Importantly, in the rapidly growing human fetus in utero, serum IGFBP-1 concentrations, which have not previously been measured by RIA, were not generally increased. Serum IGFBP-1 expression is inhibited by insulin postnatally (46), and IGFBP-1 concentrations are increased rapidly by shortterm fasting (4749). Whether factors like low maternal nutritional intake before delivery and restricted placental blood and nutrient flow during delivery and stress (50) may result in increased serum IGFBP-1 in the newborn is not known.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of Insulin-Like Growth Factor-Binding Protein-1, −2, and −3: Quantitative Measurements by Radioimmunoassay in Human Fetal Serum

et al. 1994

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Section: Discussionmentioning

confidence: 99%

Ontogeny of Insulin-Like Growth Factor-Binding Protein-1, −2, and −3: Quantitative Measurements by Radioimmunoassay in Human Fetal Serum

et al. 1994

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“…From a clinical point of view, this makes IGFBP-1 at admission an interesting prognostic predictor, which also remained after multiple adjustment. IGFBP-1 has been described as the most likely acute regulator of IGF-I actions (25), and the hepatic production of IGFBP-1 is upregulated in response to proinflammatory cytokines (26) and physiological stresses (27) and is downregulated by insulin (13). There are several potential links between high levels of IGFBP-1 and increased cardiovascular risk.…”

Section: Baseline Characteristicsmentioning

confidence: 99%

“…Thus, it is of interest to explore the IGF-I system as a potential novel risk factor and as a possible link between type 2 diabetes and subsequent cardiovascular complications (12). The hepatic production of IGFBP-1 is downregulated by insulin (13). Accordingly, in the general population, there is a correlation between low levels of IGFBP-1 and hyperinsulinemia, and these findings may link to an increased cardiovascular risk (14,15).…”

mentioning

confidence: 99%

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

et al. 2007

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OBJECTIVE -There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGFbinding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes. RESEARCH DESIGN AND METHODS -The Diabetes MellitusInsulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available. CONCLUSIONS -High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI. RESULTS Diabetes Care 30:2343-2348, 2007P atients with type 2 diabetes have an increased risk for cardiovascular disease (CVD) (1). The prognosis after an acute myocardial infarction (AMI) does, indeed, already deteriorate at glucose levels in the upper normal range (2,3). The importance is underlined by the high prevalence of AMI patients with previously undetected glucose abnormalities (4 -6). The increased cardiovascular risk cannot be completely explained by traditional risk factors, and mechanisms amplifying their impact are not fully understood (7). Thus, the search for novel risk factors linking type 2 diabetes and CVD is important (8).The IGF-I system has been related to poor glucose control, and low levels of IGF-I have been related to future type 2 diabetes (9). In addition, the IGF-I system and especially low IGF-I, low IGF binding protein (IGFBP)-1, and high IGFBP-3 relate to increased cardiovascular risk (10,11). Thus, it is of interest to explore the IGF-I system as a potential novel risk factor and as a possible link between type 2 diabetes and subsequent cardiovascular complications (12). The hepatic production of IGFBP-1 is downregulated by insulin (13). Accordingly, in the general population, there is a correlation between low levels of IGFBP-1 and hyperinsulinemia, and these findings may link to an increased cardiovascular risk (14,15). However, IGFBP-1 concentrations rise during the development of type 2 diabetes, despite persisting hyperinsulinemia, indicating increased hepatic insulin resistance during disease progression (16,17). These observations were supported by van den Berghe et al. (18), who demonstrated that patients admitted to the intensive care unit with elevated levels of IGFBP-1 presented a poor prognosis regarding mortality, a finding that related to acute hepatic insulin resistance. Furthermore, there is a correla...

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“…Of the six IGFBP, IGFBP-1 is the only one that displays rapid dynamic regulation in vivo, with serum levels varying 10-fold or more in relation to meals. Plasma IGFBP-1 is increased by fasting (Busby et al 1988;Cotterill et al 1988), malnutrition (Straus & Takemoto 1990;Donovan et al 1991) and diabetes (Brismar et al 1988;Suikkari et al 1988). IGFBP-1 is mainly synthesized by the liver, and in vivo its expression is mainly controlled by insulin, growth hormone and glucose.…”

Section: An Example Of Amino Acid Limitation: Protein Undernutritionmentioning

confidence: 99%

Amino acid limitation regulates gene expression

1999

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In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

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Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus

Cited by 160 publications

References 15 publications

Ontogeny of Insulin-Like Growth Factor-Binding Protein-1, −2, and −3: Quantitative Measurements by Radioimmunoassay in Human Fetal Serum

Ontogeny of Insulin-Like Growth Factor-Binding Protein-1, −2, and −3: Quantitative Measurements by Radioimmunoassay in Human Fetal Serum

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

Amino acid limitation regulates gene expression

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