Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition.

The hierarchy of diet components (e.g., protein, carbohydrate, vitamins, and minerals) influencing growth hormone (GH), insulin-like growth factor-I (IGF-I), and their binding proteins (BP) is not well defined. Young adult rats were fed diets for 1 mo that included low protein or 60% and 40% of carbohydrate calories. We hypothesized that levels of both hormones, their dominant BPs and liver IGF-I mRNA would fall, and that part of the mechanism for decreasing serum IGF-I would be enhanced IGFBP-3 protease activity. By day 30, caloric deprivation to 40% lowered serum GH, GHBP, IGF-I and IGFBP-3, and liver IGF-I mRNA. This was the only condition resulting in body weight loss (-15%) vs 39% gain in controls. Restriction to 60% calories had no impact on BP levels, slightly lowered IGF-I (-12%) in the face of a 95% inhibition of GH levels, while allowing a modest 9% body weight gain. Protein deprivation lowered serum GH, IGF-I and IGFBP-3, and liver IGF-I mRNA, while GHBP levels were normal. The reduced total IGF-I under these dietary conditions could not be explained by an increase in IGFBP-3 protease activity, or a decrease in the association of IGF-I with IGFBP-3 and the acid labile subunit.     

早孕妇女血清IGF-Ⅰ、IGFBP-3检测临床意义分析

目的 探讨早孕妇女血清胰岛素样生长因子Ⅰ(IGF-Ⅰ)、胰岛素样生长因子结合蛋白3 (IGFBP-3)含量检测的临床意义.方法 选择体外受精与胚胎移植术(IVT-ET)患者,以术后第14天人绒毛膜促性腺激素β亚基(β-HCG)阴性者为试验组A (30例),β-HCG>650.00 mIU/mL为试验组B (30例).以健康孕6周妇女为试验组C( 30例).测定各组IGF-Ⅰ、IGFBP-3.结果 试验组B血清IGF-Ⅰ、IGFBP-3含量低于试验组A(P<0.05);试验组C IGF-Ⅰ高于试验组A及试验组B(P<0.05);试验组C IGFBP-3与试验组A无统计学差异(P＞0.05),但高于试验组B(P<0.05);IGF-Ⅰ、IGFBP-3呈正相关(r=0.766 7).结论 IVT-ET术后14 d,孕妇血清IGF-Ⅰ、IGFBP-3含量均偏低;随孕期延长、胎盘形成,IGF-Ⅰ、IGFBP-3含量迅速增加.孕妇血清IGF-Ⅰ、IGFBP-3可用于预测胚胎发育、胎儿生长状况.     

Age- and growth hormone-induced alterations in renal sulfate transport.

The effects of growth hormone (GH) treatment on renal sodium sulfate cotransport (NaSi-1) were studied in adult (9-10 months) and old (22-23 months) male Fischer 344 rats. All animals received twice-daily s.c. injections of recombinant human GH (hGH; 4 mg/kg) for up to 6 days. Animals were sacrificed by exsanguination on days 0, 1, 2, 3, 4, 5, and 6. Kidneys were removed, and kidney cortex was trimmed immediately and used for RNA and membrane preparations. Plasma hGH concentrations were significantly lower in old rats during the hGH treatment (P <.05). Insulin-like growth factor-I (IGF-I) levels were significantly increased and remained stable after day 2 of hGH treatment in both age groups (P <.05). There was no significant difference in plasma IGF-I levels between age groups. Plasma IGF-I binding protein 3 (IGFBP-3) concentrations were significantly higher in 9- to 10-month-old rats compared with that in 22- to 23-month-old animals (P <.001). There were no significant differences in plasma IGFBP-3 concentrations between days of hGH treatment. The NaSi-1 mRNA levels were significantly lower in 22- to 23-month-old rats compared with that in 9- to 10-month-old animals (P <.001). The NaSi-1 mRNA levels were significantly increased on days 2 and 3 of hGH treatment (P <.05) and then gradually decreased to the control value. The NaSi-1 protein levels in old animals (22-23 months) were also significantly lower than that of 9- to 10-month-old animals and were significantly increased from day 2 of hGH treatment, reaching a maximum level on day 3 or 4 and then returning to the baseline level in both age groups. From these results, it was concluded that 1) NaSi-1 mRNA and protein levels are lower in old animals and increase in both adult and aged rats after hGH treatment, 2) plasma IGF-I levels are similar in adult and aged rats and increase after hGH treatment, and 3) plasma IGFBP-3 levels are lower in old rats and remain unchanged after hGH treatment.     

Effects of ethanol on fetal fuels and brain growth in rats

The mechanism of fetal brain growth retardation caused by maternal alcoholism is unclear. In this study we examined fuel concentrations in brain and blood samples and their relationship to brain growth in term fetuses of rats fed ethanol during pregnancy. The offspring of ethanol-fed (EF) rats showed a significant decrease in body and brain weights compared with those of pair-fed (PF) control rats and control rats given free access to food (ad libitum fed) (AF). The EF and PF rats consumed nearly 20% less food than the AF rats, and both groups showed a slight but significant reduction of the maternal blood glucose level. In PF rats, beta-hydroxybutyrate concentration was increased in maternal as well as in fetal blood and brain samples, but no adverse effect of this magnitude of maternal undernutrition was observed on fetal body or brain weights. In EF fetuses, plasma glucose and pyruvate levels were decreased and lactate levels were increased, resulting in a nearly twofold increase in the lactate-to-pyruvate ratio when compared with levels in control fetuses. The beta-hydroxybutyrate--to-acetoacetate ratio was increased because of low plasma acetoacetate concentration. In EF fetuses, brain glucose and pyruvate levels were decreased. Fetal brain weight showed a positive correlation with brain glucose concentration and a negative correlation with the brain concentrations of lactate or ketones. It is surmised that an aberrant fetal fuel mixture may play a role in the fetal growth retardation associated with maternal alcoholism.     

Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3).

Assays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) have become essential tools in the diagnostic work-up of disorders of the somatotropic axis in children and adults. The aim of this study was to evaluate the automated IMMULITE IGF-I and IGFBP-3 assays and to establish reference limits--central 95% intervals, median, 0.1 and other centiles as clinically relevant--as a function of age from 797 females and 787 males, from the first week of life through the ninth decade. Pubertal children were classified by sex and by sexual maturation (Tanner stage). IGF-I and IGFBP-3 levels were also assayed in 20 pediatric patients each with growth hormone deficiency (GHD) and Turner syndrome (UTS), before and during 12 months of recombinant growth hormone (rhGH) therapy, as well as in 11 adult patients with GHD and seven with acromegaly before therapy. Both the IGF-I and IGFBP-3 assays were accurate, specific and sufficiently sensitive to measure IGF-I and IGFBP-3 in serum with good linearity and recovery. In the IGF-I assay, potential interference from IGFBPs was eliminated by blocking with excess IGF-II. Circulating IGF-I and IGFBP-3 concentrations, and their ratio IGF-I/IGFBP-3, were age-dependent, showing low levels immediately after birth, a typical pubertal peak for girls and boys, and a pronounced decline after puberty, reaching a plateau in early adulthood. In adults IGF-I and IGFBP-3 levels decreased smoothly but steadily with age. Children with GHD and UTS had low circulating IGF-I and IGFBP-3 levels which increased to normal reference limits under therapy with rhGH. Adult GHD patients showed IGF-I levels below the age-related median; untreated acromegalic patients mostly had IGF-I and IGFBP-3 levels above the age-related 97.5th centile. In conclusion, the automated IMMULITE IGF-I and IGFBP-3 assays are reliable tools in the diagnosis of pathologies of the GH/IGF axis and in the follow-up of their therapies.     

Influence of acute exercise on urinary protein, creatinine, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children

Insulin-like growth factor-I (IGF-I) is a polypeptide hormone and present in human urine. Insulin-like growth factor binding protein-3 (IGFBP-3) is the major form of binding protein in human circulation and functions as a carrier for IGF-I. Our goal was to determine the effects of volleyball exercise on the concentrations of urine protein, creatinine, IGF-I, and IGFBP-3 in children and to find out whether these effects differ between boys and girls. Volunteer children (13 females and 14 males), aged 10-13 years old were included in this work. Weight and height of the subjects were measured, and urine samples of their were collected before and after 2 hours of exercise. Urinary protein, creatinine, IGF-I and IGFBP-3 levels were analysed. Urinary protein, creatinine and IGF-I concentrations were increased after two hours of exercise wheres urinary IGFBP-3 concentrations did not change. In addition, no statistically significant difference in all parameters analysed was observed between boys and girls of similar age and body mass index.     

Serum IGF-I and IGFBP-3 in healthy pregnancies and patients with preeclampsia

DESIGN AND METHODS: We studied serum levels of IGF-I and IGFBP-3 in 68 pregnant women; 28 mild preeclampsia, 13 severe preeclampsia, and 27 healthy pregnant control subjects. RESULTS: When compared with the healthy pregnant group preeclampsia groups had markedly decreased mean serum IGF-I levels. The difference was also significant between the mild and severe preeclampsia groups. Serum mean IGFBP-3 level was also lower in both preeclampsia groups than in healthy pregnancy group, but the difference between the preeclampsia groups did not reach significance. For IGF-I/IGFBP-3 ratio, the mean levels were significantly lower in mild and severe preeclampsia groups than in healthy pregnancy group. Also the mean IGF-I/IGFBP-3 ratio was significantly lower in the severe preeclampsia group compared with the mild preeclampsia group. CONCLUSIONS: IGF-1 and IGFBP-3 levels in patients with preeclampsia were compared with healthy pregnant control subjects. IGF-I and IGF-I/IGFBP-3 ratio may be useful for estimate the severity of preeclampsia.     

Regulation of rat hepatic low density lipoprotein receptors. In vivo stimulation by growth hormone is not mediated by insulin-like growth factor I.

Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on hepatic LDL receptors are direct or mediated by insulin-like growth factor I (IGF-I). Two models were studied in which substitution with GH is important for the regulation of hepatic LDL receptors: hypophysectomized rats receiving high-dose ethynylestradiol or challenge with dietary cholesterol. The hypophysectomized rats were hormonally substituted by infusion with dexamethasone and L-thyroxine, and either GH or IGF-I. In both models, GH was essential for maintaining normal expression of LDL receptors. In contrast, despite fully normalized plasma levels, IGF-I did not support the expression of hepatic LDL receptors. Analysis of plasma lipoproteins revealed that substitution with GH, but not with IGF-I, reduced LDL and intermediate density lipoproteins. In addition, determination of hepatic mRNA levels for apo B-100 and apo B-48 indicated that GH may be more effective than IGF-I in the promotion of apo B mRNA editing. In conclusion, GH has specific effects on hepatic LDL receptor expression and plasma lipoprotein levels that are not mediated by IGF-I.     

Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease.

To determine whether chronic hypoxemia results in alterations in endocrine function that may contribute to growth failure, we measured growth hormone (GH), somatomedins (insulin-like growth factors I and II, IGF-I and IGF-2), hepatic growth hormone receptors, and circulating IGF-binding proteins IGFBP-3 and IGFBP-2 in 12 newborn lambs with surgically created pulmonic stenosis and atrial septal defect, and in 10 controls. During chronic hypoxemia (oxygen saturation of 60-74% for 2 wk), weight gain was 60% of control (hypoxemic, 135 +/- 20 vs. control, 216 +/- 26 g/d, P less than 0.02). IGF-I was decreased by 43% (hypoxemic 253.6 +/- 29.3 SE vs. control 448.0 +/- 75.5 ng/ml, P = 0.01), whereas GH was unchanged (19.9 +/- 5.1 vs. 11.9 +/- 3.0 ng/ml, NS). The increase in IGF-1 was associated with a decrease in IGFBP-3 (hypoxemic, 5.09 +/- 1.25 vs. control, 11.2 +/- 1.08 arbitrary absorbency units per mm (Au.mm), P less than 0.01), and increase in IGFBP-2 (0.47 +/- 0.03 vs. 0.19 +/- 0.13 Au.mm, P less than 0.05), but no significant downregulation of hepatic GH receptors (hypoxemic, 106.1 +/- 20.1 vs. control, 147.3 +/- 25.9 fmol/mg, NS). Thus, chronic hypoxemia in the newborn is associated with a decrease in IGF-I and IGFBP-3 in the face of normal GH. This suggests peripheral GH unresponsiveness, similar to protein-calorie malnutrition or GH receptor deficiency dwarfism, but mediated at a level distal to the hepatic GH receptor.     

Monitoring insulin-like growth factors in HIV infection and AIDS

There is a close association between the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, infection and immunity. Infection with the human immunodeficiency virus (HIV) is often associated with a decrease of the concentrations of IGF-I, IGF-II, IGF-binding protein 3 (IGFBP-3) and an increase of IGFBP-1 and -2. Many investigators have studied the relationship between the GH-IGF-I system and some of the most common characteristics of disease progression, such as decreased CD4 cell counts, weight loss and fat redistribution. Although conditions for restoration of thymic function and lymphopoiesis with GH or IGF-I are still not well defined, many studies led to the development of clinical trials on the therapeutic use of GH, IGF-I and GHRH for the treatment of weight loss or fat redistribution, two problems which persist despite the introduction of highly active antiretroviral therapy. Monitoring IGF-I concentrations during treatment with GH and GHRH is likely to become an essential component of their therapeutic use. IGF-I levels are the first indicator of treatment efficacy and can be used to monitor compliance. High levels of IGF-I are a warning sign for the increased risk of potential adverse effects, such as acromegalic-like symptoms or malignancy. This could lead to a reduction of the therapeutic dose or the temporary interruption of treatment until IGF levels reach a safe range. IGF-I levels are also likely to increase with other hormones used in HIV patients, such as erythropoietin for the treatment of anemia or anabolic androgens in HIV-infected women.     

Effect of growth hormone therapy in mitigating hypoxia-induced and food restriction-induced growth retardation in the newborn rat.

OBJECTIVE: Hypoxia may alter the neuroendocrine control of catabolic and anabolic states early in postnatal life by modulating the growth hormone-insulin-like growth factor-I (GH-IGF-I) system. We wondered: a) to what extent hypoxia effects on the GH-IGF-I axis differed from those of food deprivation alone; and b) whether administration of exogenous GH mitigates alterations of the GH-IGF-I axis caused by hypoxia or food restriction. DESIGN: Prospective laboratory investigation using nursing dams and suckling pups. Experimental groups included: a) room air control subjects; b) hypoxia-exposed subjects (FIO2, 0.12); or c) room air breathing subjects whose dam food intake was matched to that of hypoxic dams. Half of the pups in each group were administered rat GH (100 microg subcutaneously each day), and the remaining received vehicle alone. The intervention lasted 18 days. SETTING: Research laboratory in a university medical center. SUBJECTS: Twelve litters of 1-day-old Sprague-Dawley rat pups and nursing dams. INTERVENTIONS: Hypoxia exposure, food restriction, GH administration. MEASUREMENTS AND MAIN RESULTS: By the end of the study, body weights of the hypoxic and pair-fed pups were significantly lower than the weights of control animals (p < .001 for both groups), and weight gain correlated significantly with total dam food consumption (r2 = .85, p < .0001). GH administration increased weight gain only in hypoxic animals (p < .001) but it increased tail lengths significantly in both hypoxic and control pups (p < .001). Serum IGF-I levels in both hypoxic and pair-fed pups were significantly lower than in control animals. Serum IGF-binding protein-3 (IGFBP-3) was significantly lower in the hypoxic compared with the control animals. GH administration resulted in significant increases in serum levels of IGFBP-3 in both the control (p < .05) and the hypoxic (p < .01) pups compared with their vehicle-treated litter mates. CONCLUSIONS: Exogenous GH attenuates growth impairment associated with hypoxia but not with food restriction, and these effects may be mediated in part by IGFBP-3.     

Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry?

BACKGROUND: Insulin, growth hormone (GH), and growth factors (insulin-like growth factors [IGFs] and their binding proteins [IGFBPs]) are known to influence fetal growth and also the synthesis/secretion of the recently discovered hormones leptin and ghrelin. METHODS: In 153 delivering mothers and their offspring at birth, we prospectively investigated the association between mothers' and babies' serum concentrations of ghrelin, leptin, insulin, IGF-1, and IGFBP-3 and neonatal anthropometric characteristics and the growth of the fetus. We also tried to put babies' serum glucose and GH measurements in this context. RESULTS: Birth weight (BW), birth length, head circumference, and ponderal index (PI) were positively associated with cord IGF-1, IGFBP-3, and leptin and negatively associated with GH. BW was independently associated with maternal stature and prepartum weight, birth length with maternal stature, PI with maternal insulin and prepartum weight, and head circumference with maternal ghrelin. Compared with preterm infants whose development was appropriate for gestational age (AGA), preterm growth-restricted babies displayed alteration in GH-IGF axis (increased GH and low IGF-1 and IGFBP-3 concentrations), low leptin and glucose concentrations, and increased ghrelin concentrations. In large-for-gestational-age (LGA) babies, leptin, IGFBP-3, insulin, and glucose concentrations were significantly higher in asymmetric LGA newborns than in symmetric LGA and AGA newborns. CONCLUSIONS: We found relationships between metabolic factors, fetal growth, and anthropometry. Intrauterine growth restriction involved alteration in the fetal GH-IGF axis, with relatively low leptin and glucose concentrations and increased ghrelin concentrations. Leptin, insulin, and IGFBP-3 delineated subtypes of fetal overgrowth.     

Effects of octreotide on serum insulin-like growth factor I and insulin-like growth factor binding proteins in patients with cirrhosis

Hyperinsulinaemia and reduced insulin sensitivity are common features in patients with cirrhosis. Octreotide, a long-acting somatostatin analogue, is used in cirrhotic patients in the treatment of bleeding oesophageal varices. Octreotide has potent effects on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis in healthy subjects. but the effects on the GH/IGF-I axis in patients with cirrhosis have been described only briefly. The effects of a 12 h infusion of octreotide (bolus 0.75 microg/kg followed by 0.75 microg/kg/h) in 25 subjects (normals n=9, compensated cirrhotics n=8, decompensated cirrhotics n=8) were compared with those in placebo-treated controls (n=19) during fasting conditions. IGF-I, free IGF-I, IGF binding proteins (IGFBPs), insulin, C-peptide, GH and glucose were measured. Insulin resistance was calculated using the HOMA method. Octreotide reduced levels of total IGF-I in patients with compensated cirrhosis (p=0.03) and free IGF-I in decompensated cirrhosis (p<0.01). Insulin resistance was significantly reduced in normal subjects. whereas the reduction in insulin resistance did not reach statistical significance in patients with cirrhosis. In normal subjects, octreotide increased the IGFBP-1 area under curve threefold (p<0.01) and decreased IGFBP-3 levels (p<0.01), but these effects were blunted in the cirrhotic patients. Similarly, the reduction of insulin and C-peptide was blunted in the cirrhotic patients, whereas a significant reduction in GH was demonstrated in all groups. The effects of octreotide on the GH/IGF-I axis are mitigated in patients with cirrhosis and this may be a reflection of relative hyperinsulinaemia during octreotide treatment in these patients.     

Insulin-like growth factors (IGF-I, free IGF-I and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation.

Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play an important role in cell growth and differentiation. Clinical and epidemiological studies have indicated that measuring IGFs and IGFBPs in blood has potential implications in assessing growth-related abnormalities and risks of certain types of cancer. To facilitate the application, we reported a large collection of reference ranges of IGFs and IGFBPs in normal population and evaluations of these molecules in serum and plasma as well as the impact of freeze-thaw cycles on the measurement. IGF-I, IGFBP-3 andALS showed a similar pattern of change associated with age. Levels of these molecules were low at birth and increased with age through puberty. After puberty the levels declined slowly with age. Overall, IGF-I, IGFBP-3 and ALS were slightly higher in females than in males. Free IGF-I accounted for about 1% of the total IGF-I and its variation with age was similar to total IGF-I. IGF-II levels were also increased with age from birth to puberty, but became stable after puberty. There was little difference in IGF-II levels between genders. IGFBP-2 levels declined with age from birth to puberty. Levels of IGFBP-6 in contrast were increased with age. These IGF binding proteins were higher in males than in females. IGFs, IGFBP-3 and ALS were 5-10% higher in serum than in plasma. IGFBP-2 and IGFBP-6 differed substantially between serum and plasma. Freeze-thaw treatment up to five cycles had little impact on plasma levels of IGFs and IGFBP-3. Our observations suggest that levels of IGFs and their binding proteins are varied with age, gender, and types of specimen and that these variations need to be taken into consideration when IGFs and their binding proteins are utilized in clinic and research.     

Decreased serum insulin-like growth factor-I in burn patients: relationship with serum insulin-like growth factor binding protein-3 proteolysis and the influence of lipid composition in nutritional support

OBJECTIVES: To test the effects of the amount and type of fat in the nutritional support on serum insulin-like growth factor (IGF)-I concentrations in burn patients and to test the hypothesis that the serum proteolytic activity for insulin-like growth factor binding protein (IGFBP)-3 is a major mechanism for the decreased serum IGF-I observed in these patients. DESIGN: Randomized, double-blind trial of three different nutritional supports and analysis of serum IGF-I, IGFBP-3, and serum IGFBP-3 proteolysis. SETTING: Burn center in a university hospital. PATIENTS: A total of 23 severely burned (>25% total body surface area burned) adult patients. INTERVENTIONS: Patients were randomly assigned to three types of nutritional support differing in the amount of energy derived from fat and the presence or absence of fish oil: Group I (control), 35% fat; Group II, 15% fat; Group III, 15% fat with 50% as fish oil. Nutritional support was both parenteral and enteral and was started within 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Serum IGF-I and IGFBP-3 were measured by radioimmunoassay every 3 days for 28 days in 23 severely burned adults. In six patients, IGFBP-3 was measured by ligand binding assay and the serum proteolytic activity for rhIGFBP-3 was measured as well. Serum IGF-I concentration was low in all subjects throughout the study period, but did increase with time (p < .01); significantly higher values were found in Group III (p < .05). Multivariate analysis showed that fish oil and low fat solutions were significantly correlated to serum IGF-I concentrations. Serum IGFBP-3 (radioimmunoassay) was higher than normal throughout the study with no difference between the groups. Between days 4 and 16, IGFBP-3 was cleaved into two fragments in all patients studied, and the molecular weights of the fragments were equal to those observed in the serum of a woman late in pregnancy. During this period of time, serum proteolytic activity for rhIGFBP-3 was >30% in 24 of the 30 samples measured, whereas 20 of the 28 samples measured thereafter were normal (<25%). Serum IGFBP-3 concentration from ligand binding assay was correlated with serum proteolytic capacity in all subjects (mean r2 = 0.77; p < .01) and with serum IGF-I concentrations in five of six subjects (mean r2 = 0.81; p < .01). CONCLUSIONS: In burn injury, serum IGF-I concentrations are sensitive to the amount and type of fat in their nutritional support. The presence of fish oil allowed for a more rapid recovery of serum IGF-I levels. The proteolysis of IGFBP-3 may be an important cause of the decreased serum IGF-I values and the protease(s) responsible for this seem to be similar to those observed in late pregnancy.     

Effects of octreotide on serum insulin-like growth factor I and insulin-like growth factor binding proteins in patients with cirrhosis

Hyperinsulinaemia and reduced insulin sensitivity are common features in patients with cirrhosis. Octreotide, a long-acting somatostatin analogue, is used in cirrhotic patients in the treatment of bleeding oesophageal varices. Octreotide has potent effects on the growth hormone (GH )/insulin-like growth factor I (IGF-I ) axis in healthy subjects, but the effects on the GH/IGF-I axis in patients with cirrhosis have been described only briefly. The effects of a 12 h infusion of octreotide (bolus 0.75 &#119 g/kg followed by 0.75 &#119 g/kg/h) in 25 subjects (normals n = 9, compensated cirrhotics n = 8, decompensated cirrhotics n = 8) were compared with those in placebo-treated controls (n = 19) during fasting conditions. IGF-I, free IGF-I, IGF binding proteins (IGFBPs), insulin, C-peptide, GH and glucose were measured. Insulin resistance was calculated using the HOMA method. Octreotide reduced levels of total IGF-I in patients with compensated cirrhosis (p = 0.03) and free IGF-I in decompensated cirrhosis (p < 0.01). Insulin resistance was significantly reduced in normal subjects, whereas the reduction in insulin resistance did not reach statistical significance in patients with cirrhosis. In normal subjects, octreotide increased the IGFBP-1 area under curve threefold (p < 0.01) and decreased IGFBP-3 levels (p < 0.01), but these effects were blunted in the cirrhotic patients. Similarly, the reduction of insulin and C-peptide was blunted in the cirrhotic patients, whereas a significant reduction in GH was demonstrated in all groups. The effects of octreotide on the GH/IGF-I axis are mitigated in patients with cirrhosis and this may be a reflection of relative hyperinsulinaemia during octreotide treatment in these patients.     

GH-IGF轴与老年糖尿病视网膜病变的关系及其监测意义

目的　研究血清中生长激素 (GH)、胰岛素样生长因子 Ⅰ(IGF Ⅰ)及胰岛素样生长因子结合蛋白 3(IGFBP 3)与老年糖尿病性视网膜病变的关系。方法　用放射免疫方法 (RIA)测定 10 6例健康老人 ,5 9例老年糖尿病 (DM )患者(其中无糖尿病视网膜病变 (NDR) 30例 ,单纯性糖尿病性视网膜病变 (BDR) 18例 ,增殖性糖尿病视网膜病变 (PDR)11例 )及 4 5例健康成人血清中GH、IGF Ⅰ及IGFBP 3浓度。结果　健康老年人血清GH、IGF Ⅰ、IGFBP 3含量较健康成人显著降低 (p均 <0 .0 5 ) ;血清中GH、IGF Ⅰ、IGFBP 3含量随年龄增大而明显降低 ,且年龄与GH、IGF Ⅰ、IGFBP 3呈显著负相关 (r1=- 0 .4 32 0 ,r2 =- 0 .394 6 5 ,r3 =- 0 .4 12 74。P均 <0 .0 5 )。与健康老人比较 ,老年DM患者BDR、PDR组中血清中GH、IGF Ⅰ、IGFBP 3均显著升高 (P <0 .0 1) ,其升高程度与DR的严重程度显著相关。结论　检测GH、IGF Ⅰ、IGFBP 3在血清中的浓度可早期发现老年DR ,并对其病情的严重程度及判断预后有重要意义。     

Stability of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 measured by the IMMULITE automated chemiluminescence assay system in different blood specimens

Insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) are measured to diagnose disorders of the somatotropic axis in children and adults. In clinical studies samples for IGF-I and IGFBP-3 measurement must often be stored for months and sent to specialized laboratories. Therefore, we tested the stability of IGF-I and IGFBP-3 in whole blood, serum and plasma from 12 volunteers at 4 degrees, 22 degrees, and 37 degrees C for several hours and at -25 degrees C for several months. The effect of only one protease inhibitor (Aprotinin = Trasylol, Bayer, Germany ) on IGF-I and IGFBP-3 measured in the automated IMMULITE assay system (DPC, Los Angeles) was tested. IGF-I and IGFBP-3 were stable in heparinized whole blood, plasma and serum at 22 degrees C up to 24 hours. IGF-I was stabilized by aprotinin for up to 72 hours at 37 degrees C. Factor concentrations were not altered after storage at -25 degrees C for at least 12 months. Recognition of IGFBP-3 fragments by the antibody used in the automated IGFBP-3 IMMULITE was excluded by measurement in 26 sera from pregnant women which usually contain IGFBP-3 fragments. In conclusion, samples for measurement of IGF-I and IGFBP-3 should be kept on ice and cooled if shipment takes more than 48 hours or alternatively 5000 IU/ml aprotinin should be added. IMMULITE assays are also valid to measure IGF-I and IGFBP-3 after at least 12 months storage at -25 degrees C.