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K Brismar

Publications and source records attributed to K Brismar.

At least 19 recordsLinked to original sources
PubMed1997

Genetic and environmental architecture of the features of the insulin-resistance syndrome.

The contribution of genetic and environmental effects to the clustering of metabolic factors contained in insulin-resistance syndrome (IRS) is still unclear. To explore the genetic architecture of IRS, we examined a population of elderly twins from the Swedish Adoption/Twin Study of Aging. A sample of 289 pairs of twins (mean age 65.5 years; range 52-86 years), of whom 140 pairs had been reared apart, was studied. The features contained in the IRS consisted of body-mass index (BMI), insulin resistance, triglycerides, HDL cholesterol, and systolic blood pressure. Intraclass correlations, cross-twin correlations, and model-fitting analyses were used to evaluate the relative importance of genetic and environmental influences for variation in and covariation among the components of the syndrome. All of the five principal metabolic components contained in IRS are more or less influenced by a single latent genetic factor, whereas only three of the components (triglycerides, insulin resistance, and HDL cholesterol) are influenced by a latent individual-specific environmental factor. The genetic factor reflected influences of importance to BMI and insulin resistance and to a lesser degree to triglycerides, HDL cholesterol, and systolic blood pressure, whereas the individual-specific environmental factor reflected influences in common to triglycerides and HDL cholesterol and to a lesser degree to insulin resistance. Systolic blood pressure was related to IRS, albeit weakly, only through genetic effects. In conclusion, IRS appears to be influenced by different sets of genetic and environmental mechanisms. The set of genetic influences in common to all the components may initiate the abnormalities underlying IRS.

Aged↗
PubMed1996

Altered properties of the fibrin gel structure in patients with IDDM.

High plasma fibrinogen levels are associated with vascular complications in the general population. Fibrin, the structural element in a clot, is derived from fibrinogen by activation of thrombin. An abnormal fibrin gel structure has been demonstrated in patients with myocardial infarction and in diabetic patients during poor metabolic control. In the present study the properties of fibrin gel structure were investigated in 20 patients with insulin-dependent diabetes mellitus (IDDM): 10 patients without (age: 30 +/- 8; diabetes duration: 7 +/- 6 years), and 10 patients (age: 44 +/- 7; diabetes duration: 27 +/- 9 years) with microangiopathy. Fifteen healthy subjects served as controls (age: 40 +/- 8 years). The glycosylated haemoglobin level (HbA1c) was elevated (p < 0.001) in the patients: 6.5 +/- 1.5% in diabetic patients without, and 7.1 +/- 1.0% in diabetic patients with microangiopathy. C-reactive protein and plasma fibrinogen were similar as compared to healthy control subjects. The properties of the fibrin gel structure; i.e. the permeability coefficient (Ks) and the fibre mass length ratio (mu) formed in recalcified plasma on addition of thrombin were investigated. Ks was decreased in the diabetic patients, with (6.5 +/- 2.0 cm2; p < 0.01) and without microangiopathy (6.5 +/- 2.7 cm2; p < 0.05), as compared to healthy subjects (10.0 +/- 3.4 cm2), while mu was not significantly (p = 0.14) altered. The results indicate a lower fibrin gel porosity in patients with IDDM, despite normal plasma fibrinogen and irrespective of microangiopathy. The abnormal fibrin gel structure may be due to an increased glycosylation of the fibrin (-ogen) molecule caused by long-term hyperglycaemia and may be of importance for the development of angiopathy in diabetic patients.

Adult↗
PubMed1996

Quantitative genetic analyses of insulin-like growth factor I (IGF-I), IGF-binding protein-1, and insulin levels in middle-aged and elderly twins.

With the use of quantitative genetic models, the relative importance of genetic and environmental influences on serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin was evaluated in 248 pairs of middle-aged and elderly Swedish twins reared apart and reared together. Heritability estimates (the relative influence of genetic effects) were 48% for insulin, 63% for IGF-I, and 36% for IGFBP-1. There was no indication of differences in heritability estimates for IGF-I, IGFBP-1, and insulin across age and gender groups. Nonshared environmental influences, unique to individuals, explained the remaining variance in the measures. The genetic influences on IGF-I levels were independent of the genetic influences on insulin and IGFBP-1 levels. However, a small, but significant, proportion of the genetic variation in IGFBP-1 was in common with genetic influences for insulin. Furthermore, genetic effects explained 36% of the phenotypic correlation between IGFBP-1 and insulin, whereas the phenotypic associations between IGF-I and both IGFBP-1 and insulin were entirely attributable to environmental effects. Finally, the phenotypic association between IGF-I and IGFBP-1 was mediated wholly by environmental influences in common with insulin.

Aged↗
PubMed1996

Decreased bioavailability of insulin-like growth factor-I, a cause of catabolism in hemodialysis patients?

The aim of this study was to investigate the influence of hemodialysis on insulin-like growth factor-I (IGF-I) and the IGF binding proteins (IGFBPs) in patients with end-stage renal disease (ESRD). IGF-I and IGF-II circulate bound to IGFBPs which are known to influence the IGF-I bioavailability. Ten ESRD patients were studied before and after hemodialysis on low flux filters. IGF-I, insulin and IGFBP-I were measured by specific RIAs, and IGFBP-2 and IGFBP-3 were quantified by densitometry after Western ligand blotting. Diurnal curves of IGFBP-1 were performed in two additional patients. Before dialysis, the mean (+/- SEM) IGF-I level was 202.2 +/- 12.1 micrograms/l corresponding to a SD-score of 1.8 +/- 0.3. Basal IGFBP-1 was increased 2-fold compared to normal levels (82.4 +/- 24.1 micrograms/l) and increased further during hemodialysis to 118.1 +/- 28.5 micrograms/l (P < 0.007). The mean increase during dialysis in IGFBP-1 was 74 +/- 24%. Predialysis IGFBP-2 was increased to 184.8 +/- 32.5% of the reference serum and was not significantly changed by dialysis. The predialysis IGFBP-3, 38.5 kDa band was within normal levels 90.1 +/- 18.8% of the reference serum while the IGFBP-3, 41.5 kDa band was decreased to 62.4 +/- 11.3% of the reference serum. Both IGFBP-3 bands were not significantly changed after dialysis. The mean basal insulin level was high, 38.2 +/- 3.0 mU/L, in spite of normal glucose levels suggesting insulin resistance. The mean values of IGF-I, insulin and glucose were unchanged after dialysis. The ratio between IGF-I and IGFBP-1 decreased significantly after dialysis to 53% of the ratio before dialysis (P < 0.005). The ratio between IGF-I and IGFBP-2 or IGFBP-3 did not change after dialysis. The circadian variation of IGFBP-1 during dialysis days was impaired with a delayed decrease of IGFBP-1 compared to the non-dialysis day. In ESRD patients predialysis mean values of insulin, IGF-I SD-score, IGFBP-1 and IGFBP-2 were increased, while the mean densitrometric values of the IGFBP-3 bands on Western ligand blot were either normal or reduced. IGFBP-1 was raised significantly with a mean of 74% after dialysis, the predialysis level was more than 2-fold elevated with impaired circadian variation of IGFBP-1 on dialysis days. High levels of IGFBPs may bind free IGF-I and decrease IGF-I bioavailability thus contributing to the catabolism associated with dialysis.

Adult↗
PubMed1995

[Insulin-like growth factors. Future treatment in catabolism?].

Growth is the result of complex interactions between nutrition, stimulating and inhibiting signal substances, and target cell response to these substances. The insulin-like growth factors, IGF-I and IGF-II, are important growth factors throughout life, and function both as endocrine and paracrine hormones. Their anabolic and growth promoting actions are mediated via the IGF-I receptor, present in all cells apart from liver and adipose cells, which contains the homologous insulin receptor. IGF-I expression is regulated both by nutrition and by other hormones such as insulin and growth hormone (GH), though GH regulation of IGF-I first starts after birth when growth becomes GH- dependent. Treatment with recombinant IGF-I has been shown to normalise growth in children with GH receptor deficiency. IGF peptides in serum and other fluids are always associated with binding proteins (IGFBPs). A family of six polypeptides have been characterised. The various IGFBPs have been suggested to function as storage or transport proteins, or modulators of IGF action on target cells. Proteases which cleave IGFBPs are assumed to increase the bioavailability of IGFs. Most of the IGFs in serum are bound to the GH-dependent IGFBP-3 in ternary complexes which cannot leave the circulation. The serum IGF-I concentration manifests an age-dependent pattern, mainly owing to the age-dependent level of GH production. After increasing during puberty, IGF-I levels then decrease with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Skin capillary circulation severely impaired in toes of patients with IDDM, with and without late diabetic complications.

We have recently shown that the skin microcirculation of toes is significantly impaired in patients with diabetes and peripheral vascular disease, and this may be one major reason why these patients are highly susceptible to developing skin ulcers. The aim of the present study was to investigate whether the skin microcirculation is impaired also in diabetic patients free from macroangiopathy. One foot in each of 20 patients with insulin-dependent diabetes was investigated: 10 patients with and 10 patients without late complications. All patients had normal arterial circulation of their lower extremities. Two groups of age- and sex-matched healthy subjects served as controls. The capillary blood cell velocity in the nailfold of the great toe was investigated by computerised videophotometric capillaroscopy, and the total microcirculation within the same area evaluated by laser Doppler fluxmetry. The capillary blood cell velocity and the total skin microcirculation were studied during rest, and during postocclusive reactive hyperaemia. The total microcirculation was similar in patients and control subjects, whereas the capillary circulation was markedly reduced (p < 0.01) in the patients. The ratio between the capillary and total microcirculation was significantly decreased (p < 0.05-0.01) in the patients as compared to the control subjects, indicating a local maldistribution of blood in the skin microcirculation of the diabetic patients. The results of the present study show that in spite of a normal total skin microcirculation in the toes of insulin-dependent diabetic patients, both with and without late complications, the nutritional capillary circulation is severely impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Regulation of IGFBP-1 in humans.

IGFBP-1 secretion in humans is regulated by insulin and the counter-regulatory hormones with a high production rate and rapid turnover. The IGFBP-1 fasting levels are both genetically and environmentally determined. Serum IGFBP-1 levels may be regulated by so far unknown factors during certain conditions. The fasting IGFBP-1 level can be used as a marker of diurnal IGFBP-1 and insulin secretion.

Diabetes Mellitus↗
PubMed1995

Disturbed anabolic hormonal patterns in burned patients: the relation to glucagon.

OBJECTIVE: Complex changes in the anabolic regulators of metabolism occur after major injury. We have studied the time course for IGF-I and IGFBP-1 after burn injury and their relations to circulating levels of other anabolic and catabolic hormones. The hormonal patterns during the onset of sepsis were also investigated. PATIENTS: Eight patients (age 36 (6) years, mean (SEM)) with major burn injury (burn area 42 (6) %) were studied. The first 2 days since the burn were used for rehydration therapy (rehydration period), after which a complete total parenteral nutrition (TPN) period was initiated. Seven positive blood cultures, during the study period. Six of the eight survived. MEASUREMENTS: The hormonal changes determined in the morning during the first 7 days after the burn and from day 22 to 24 were investigated. The superimposed effects of sepsis were studied by normalizing all data to the day of positive blood cultures and clinical onset of sepsis. RESULTS: On admission, plasma levels of glucagon, IGFBP-1 and GH were elevated while levels of IGF-I were low. During the first week after the burn, morning levels of glucagon and insulin increased while levels of GH and IGF-I decreased. GH levels were still elevated compared to healthy subjects. Despite the increase in insulin levels, IGFBP-1 remained elevated. Three weeks after the burn injury, IGF-I levels were increased but still markedly below normal, while IGFBP-1 levels remained unchanged. Persistent elevations of insulin levels were combined with reductions in glucagon levels. Admission levels of IGFBP-1 correlated to nitrogen loss (negative nitrogen balance) during the first 24 hours after the burn (r = 0.84, P < 0.05). A correlation between negative nitrogen balance and glucagon levels was found during early catabolic period in the rehydration period (i.e. days 2-3, r = 0.84, P < 0.01). The relative change in IGFBP-1 levels in the rehydration period correlated to changes in glucagon levels (days 2-3 vs admission, r = 0.85, P < 0.05). The insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both the rehydration period (days 2-3, r = 0.77, P < 0.05) and the third week after the burn (r = 0.77, P < 0.05). During the most catabolic phase in the first week after the burn (TPN period) there was an inverse relation between IGF-I and IGFBP-I and glucagon (r = 0.83, P < 0.05). During the less catabolic third week after the burn, an inverse correlation was found between IGF-I and glucagon (r = -0.83, P < 0.05). Sepsis, superimposed upon the burn trauma, was associated with transient elevations in IGFBP-1 and reductions in insulin despite elevated levels of glucose and a further 50% increase in nitrogen losses. CONCLUSIONS: The present findings show that marked changes is important anabolic regulating factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the attenuation of the inhibitory effects of insulin on IGFBP-1, both contribute to the reduction in IGF-I levels and bioavailability, factors which may play an important role in post injury metabolism. Furthermore, these data suggest that the catabolic hormones (catecholamines, cortisol and glucagon), primarily glucagon seem to be involved in the modulation of IGF-I and IGFBP-1 levels following burn injury.

Adult↗
PubMed1995

Skin capillary circulation is more impaired in the toes of diabetic than non-diabetic patients with peripheral vascular disease.

The aim of the present study was to investigate if diabetes negatively influences the skin microvascular reactivity in the toes of patients with peripheral vascular disease (PVD). Twenty healthy subjects, 20 diabetic, and 20 non-diabetic patients with PVD participated. One foot in each subject was investigated. The patient groups were matched for age, sex, and toe pressure. The capillary blood cell velocity in the nailfold of the great toe was investigated by videophotometric capillaroscopy, and the total skin microcirculation within the same area by laser Doppler fluxmetry. Capillary blood cell velocity and laser Doppler flux were studied during rest, and following a 1 min arterial occlusion at the toe base. The skin microvascular reactivity was impaired in both diabetic and non-diabetic patients. In the diabetic patients the disturbances were mainly seen in the capillaries, and the capillary blood flow was severely reduced during reactive hyperaemia (p < 0.01). In contrast, the total skin microcirculation was normal, indicating that sufficient blood reaches the area, but does not come out into the capillaries. The ratio between capillary blood cell velocity and laser Doppler flux, representing the distribution of blood between nutritional and non-nutritional blood compartments, was reduced in the diabetic patients (p < 0.05). These findings may contribute to the higher risk for development of chronic foot ulcers in diabetic patients with PVD.

Aged↗
PubMed1995

Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects.

To investigate whether previously reported increased levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in GH-deficient patients only reflect decreased levels of insulin or are elevated in relation to insulin, diurnal profiles of IGFBP-1 and insulin were determined in plasma from patients with GH levels below 0.2 microgram/L throughout 24 h (n = 23) and compared to profiles from patients with insulin-dependent diabetes mellitus (IDDM; n = 9) and healthy subjects (n = 12). Samples were drawn using a continuous withdrawal technique at 20-min intervals. Levels of IGF-I were determined in one morning sample. As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as well as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning. Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 micrograms/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 micrograms/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 micrograms/L, respectively). Fasting levels of IGFBP-1 correlated to 24-h mean values of IGFBP-1 in all groups separately and in the combined group (r = 0.931; P < 0.001). An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001). Corresponding values for healthy subjects were r = -0.548; P = 0.065 and r = -0.712; P < 0.01, respectively, whereas in IDDM patients the relationship was nonsignificant. Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05). When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared. However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively). The majority of the IDDM patients had values in the same range as the GH-deficient patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects.

In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted with the significant decrease in IGF-I concentrations in NOB subjects (37%; P < 0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01). Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects. IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged by fasting, as determined by RIA and Western ligand blot analysis. In accordance, no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated. Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand blot analysis was decreased in NIDDM in accordance with the finding of increased IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and modulation of GH induction of IGF-I by insulin resistance could contribute to low basal IGF-I levels and lack of a IGF-I response to fasting in patients with NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by IGFBP-3, is not likely to be altered by short term fasting, suggesting that the decrease in serum IGF-I concentrations is a result of decreased IGF-I production.

Adult↗
PubMed1994

Increased proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3) in noninsulin-dependent diabetes mellitus serum, with elevation of a 29-kilodalton (kDa) glycosylated IGFBP-3 fragment contained in the approximately 130- to 150-kDa ternary complex.

Insulin-like growth factor-I (IGF-I) in serum is predominantly bound in a ternary complex, consisting of IGF peptide, IGF-binding protein-3 (IGFBP-3), and an acid-labile subunit, or a binary complex, consisting of IGF peptide and any of the six IGFBPs. In the binary complex, IGF-I is more bioavailable and has a faster turnover rate. Proteolysis of IGFBP-3 may alter the distribution of IGF-I between these complexes by reducing IGFBP-3 affinity for IGF-I and/or acid-labile subunit and may offer an additional mechanism for regulation of IGF availability. In the present study, sera from patients with noninsulin-dependent diabetes mellitus (NIDDM) were found to have significantly higher IGFBP-3 proteolytic activity than sera from age-matched healthy subjects (188 +/- 12% vs. 104 +/- 6% of a control serum pool; P < 0.001). The mean (+/- SE) of serum IGFBP-3 levels determined by Western ligand blotting was lower in NIDDM patients than in healthy control subjects (61.5 +/- 5% and 79 +/- 5% of a control serum pool, respectively; P < 0.01). However, IGFBP-3 concentrations determined by RIA did not differ. This discrepancy could be explained by IGFBP-3 proteolysis, resulting in IGFBP-3 fragments that are detectable by RIA, but not by Western ligand blotting. Western immunoblotting of sera with or without prior treatment with endoglycosidase-F demonstrated that a glycosylated 29-kilodalton (kDa) IGFBP-3 form with a protein core of 20 kDa was present in sera from healthy controls, and this fragment was increased in NIDDM and term pregnancy sera, suggesting that it is produced by endogenous proteolysis. The presence of the 29-kDa IGFBP-3 proteolytic fragment at about 130-150 kDa after neutral size chromatography of pooled sera may suggest that 29-kDa IGFBP-3 participates in ternary complex formation. Further studies are required to determine whether the avidity of ternary complex formation with the 29-kDa IGFBP-3 fragment is reduced and whether the resulting increased IGF turnover can explain the reduced IGF-I levels (z scores) observed in NIDDM patients compared to healthy subjects (-0.81 +/- 0.32 SD vs. +0.26 +/- 0.17 SD; P < 0.001). Neutral size-chromatography of sera demonstrated that IGFBP-3 protease activity in the approximately 130- to 150-kDa mol wt range is regulated by NIDDM and pregnancy in parallel with that of unfractionated sera.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes.

Insulin-like growth factors (IGFs) circulate attached to binding proteins (IGFBPs). Only the unbound form of IGF is suggested to be biological active. The main source of circulating IGF-I and IGFBP-1 is considered to be the liver, but that of circulating IGFBP-3 is not known. IGF-I and IGFBP-3 are GH dependent, whereas IGFBP-1 is insulin regulated. The aim of the present study was to examine the effect of insulin on the hepatic secretion of IGFBP-1, IGFBP-3, and IGF-I. Seven insulin-dependent diabetic patients in whom insulin was withheld for 12 h were studied in the overnight fasted state. Blood was sampled simultaneously from the hepatic vein, a peripheral vein, and an artery before and during insulin infusion for 3 h. The basal IGFBP-1 levels in the peripheral vein were several-fold elevated (249 +/- 44 micrograms/L) compared to those in healthy subjects (37 +/- 2 micrograms/L). Fasting IGFBP-1 concentrations were inversely correlated to the insulin levels (r = -0.918; P < 0.001). The mean IGF-I concentration (175 +/- 17 micrograms/L; -1.62 +/- 0.38 SD score) was decreased compared with that in age-matched healthy subjects. The basal IGFBP-3 levels in the peripheral vein (4.50 +/- 0.33 mg/L) were within the normal range. There was a significant correlation in the hepatic vein between fasting IGF-I and IGFBP-3 levels (r = 0.928; P < 0.001). Basal splanchnic IGFBP-1 production was 18 +/- 7 micrograms/min, whereas no basal net exchanges of IGF-I or IGFBP-3 were observed across the splanchnic area. Insulin inhibited splanchnic IGFBP-1 production within 120 min and glucose output within 20 min. Serum IGF-I, but not IGFBP-3, concentrations increased significantly during the insulin infusion. In summary, this study demonstrates the existence of considerable IGFBP-1 production from the liver during insulinopenia and the complete blocking of splanchnic IGFBP-1 production and increases in serum levels of IGF-I by insulin despite no effect on IGFBP-3 levels. Thus, insulin may play a role in determining the bioavailability of IGF-I.

Adult↗
PubMed1994

Immunoreactive proinsulin-like growth factor-II levels in healthy subjects, patients with growth hormone deficiency, and patients with type 1 diabetes: effects of insulin-like growth factor-I and insulin.

Proinsulin-like growth factor-II (IGF-IIE), with an E-peptide elongation at the C-terminal, is found in the circulation and in different body fluids with mol wt between 10-16 kilodaltons compared to native 7.4-kilodalton IGF-II. Some tumors overexpress IGF-II and IGF-IIE with increased levels in patients serum, sometimes causing hypoglycemia (nonislet cell tumor-induced hypoglycemia). We have developed a RIA for a 15-amino acid part of the E-peptide. By using the E16-peptide as the labeled ligand, this RIA is unaffected by the presence of IGF-binding protein in the samples. Gel chromatography under acid and neutral conditions revealed that all IGF-IIE was detected without prior separation of serum. Using recombinant IGF-IIE21 as standard, we determined normal levels in 70 males and 67 females between 20-70 yr of age. The average was 46.6 +/- 1.1 micrograms/L, and the 95% confidence interval was between 21.4-71.9 micrograms/L. A significantly higher level was found in males (49.0 +/- 1.6 micrograms/L) compared to females (44.2 +/- 1.3 micrograms/L). In two nonislet cell tumor-induced hypoglycemia patients, levels of immunoreactive (ir) IGF-IIE were 2.5-3 times normal levels. GH-deficient patients had normal levels, but daily sc injections of recombinant human IGF-I decreased serum irIGF-IIE by 40%. Insulin-dependent diabetic patients undergoing liver venous catheterization had normal basal levels of irIGF-IIE in peripheral blood. A 180-min insulin infusion decreased the levels significantly in the vena hepatica, but no splanchnic gradient was observed.

Adult↗
PubMed1993

Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.

Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6). Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min. IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)]. The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations. When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001). In GH-deficient patients, serum GH concentrations remained undetectable (< 0.2 micrograms/L), and IGF-I concentrations were unchanged after the glucagon injection. In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min. In conclusion, glucagon increased serum IGFBP-1 concentrations in spite of increases in glucose and insulin. These results suggest that glucagon is a stimulator of IGFBP-1.

Adult↗