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E R Froesch

Publications and source records attributed to E R Froesch.

At least 109 records · Page 6Linked to original sources
PubMed1987

Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults.

Insulin-like growth factor I (IGF I) is structurally similar to insulin and shares many of its biologic properties. We compared the short-term metabolic effects of recombinant IGF I (100 micrograms [13.3 nmol] per kilogram of body weight) and insulin (0.15 IU [1 nmol] per kilogram) in eight healthy volunteers (four men and four women). The hypoglycemic responses to both hormones were nearly identical in the doses used. The lowest blood glucose levels were reached after 30 minutes: 1.98 +/- 0.44 mmol per liter after IGF I and 1.78 +/- 0.29 after insulin. On a molar basis, IGF I was only 6 percent as potent as insulin in the production of hypoglycemia. Insulin also inhibited lipolysis more effectively than IGF I. Levels of epinephrine, norepinephrine, growth hormone, glucagon, and cortisol responded similarly to both agents. The hypoglycemia produced by IGF I is probably due to the supraphysiologic concentrations of the free peptide that result from its rapid intravenous injection. Fifteen minutes after injection, the serum level of IGF I increased from 144 +/- 38 ng per milliliter at base line to 424 +/- 56, of which 80 percent was free in the plasma (not bound to IGF carrier proteins). The determination of whether any of the short-term metabolic effects of IGF I have any clinical application will require further investigation.

Adult↗
PubMed1987

Osteoblastlike cells in a serum-free methylcellulose medium form colonies: effects of insulin and insulinlike growth factor I.

Osteoblastlike (OB) cells obtained from a heterogeneous primary cell population by enzymatic cell digestion of calvaria of newborn rats are grown in a serum-free viscous alpha-MEM/F-12 medium containing 0.8% methylcellulose. In contrast to cell monolayers in conventional tissue cultures OB cells proliferate into colonies of rounded-up cells to form morulalike spherical cell clusters containing up to 100 cells. These colonies, with different cell numbers, are clearly not fibroblastlike since fibroblasts from the same rats always grow as a cell monolayer. Alkaline phosphatase activity and cAMP responsivness to PTH are expressed more markedly (70% and 250% respectively) by OB cells in the described culture system than in conventional tissue cultures. Rounded-up OB cells sediment and colonies stick to the dish; proliferation of OB cells is favored and starts 3-4 days after inoculation. Increasing concentrations of insulinlike growth factor (IGF) I (0.4-35 nM) and insulin (20-660 nM), as well as increasing initial cell density, enhances mitogenic activity of these cells in a dose-dependent way. On a molar ratio IGF I (physiological concentrations) is 10 times as potent as insulin (pharmacological concentrations) with respect to proliferation. If less than 10(5) cells/ml are inoculated, there exists an apparent relationship between initial cell density and major onset of replication, indicating the presence and accumulation of local growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1987

Insulin-like growth factor I and II in 14 animal species and man as determined by three radioligand assays and two bioassays.

Insulin-like growth factor I and II (IGF I and II) were determined by five different assays in human serum, in the sera of ten mammalian species and in chicken, turtle, and frog serum. Sera of all tested mammals contain two different IGFs corresponding to human immunoreactive IGF I and receptor reactive IGF II. Receptor reactive IGF II of most animal species does not show significant cross-reactivity in the RIA for human IGF II. IGF activity was also detected in sera of non-mammals, such as chicken and turtles, but not in frog serum. The IGF values obtained with the different assay system corresponded rather well: there is a good correlation between the values obtained in the protein binding and the fat cell assay, and between the results of the latter assays and the sum of immunoreactive IGF I and receptor reactive IGF II. The results suggest that those regions in the IGF I and II molecules which are responsible for reactivity with the type I IGF and the insulin receptor have not essentially changed during evolution. Similarly, the C-region, which mainly determines the immunological properties of IGFs, appears to have remained relatively constant in the IGF I, but not in the IGF II molecule.

Animals↗
PubMed1987

Pre-operative treatment of 5 acromegalics with a somatostatin analogue: endocrine and clinical observations.

Five acromegalic patients were treated preoperatively over a period of 1-4 weeks with the somatostatin analogue SMS 201-995. The patients received daily 3 X 100 micrograms of SMS 201-995 subcutaneously. This schedule resulted in a rapid improvement of the clinical symptoms in 4 out of 5 patients. In these same patients plasma growth hormone concentrations decreased markedly. However, only in one patient were growth hormone concentrations normalized. Plasma IGF I, which was elevated in all patients, was normalized only in this same patient. Tumour volume as determined by thin section CT-scans decreased only in one case by 17%. All tumours appeared extraordinarily soft upon operation. Conventional light microscopy showed no difference between tumours of SMS-pre-treated and untreated patients. Ultrastructural investigation showed the usual heterogeneity.

Acromegaly↗
PubMed1986

[Acromegaly and insulin-like growth factors].

The insulin-like growth factors (IGF) I and II are structural homologues of insulin with a molecular weight of 7500. In contrast to insulin, their insulin-like effects are not suppressible by insulin antibodies. They are mainly produced by the liver under the influence of growth hormone and are bound to specific carrier proteins in the circulation. According to the somatomedin concept, they mediate the effects of growth hormone on growth. IGF I is identical to somatomedin A and somatomedin C. In acromegalic patients oversecretion of growth hormone is accompanied by a significant increase in the serum IGF I level, whereas IGF II levels are normal. IGF I can, therefore, serve as a useful additional laboratory index in the diagnosis of acromegaly and in evaluating successful surgery and/or radiotherapy of this disease. Bromocriptine therapy often improves the clinical symptoms of acromegaly and lowers growth hormone levels without normalizing IGF I. In most of these patients, however, suppression of growth hormone under oral glucose load is not normal. In our opinion the determination of IGF I should not replace growth hormone determinations during an oral glucose tolerance test; rather, it should be performed to complement this test, above all when its results cannot be unambiguously interpreted.

Acromegaly↗
PubMed1986

Glucose uptake and phosphorylation in fat cells of fasted and hypophysectomized rats.

Fat cells of hypophysectomized and fasted rats metabolize 10 times less glucose than adipocytes of normal rats in the presence of insulin. Glucose transport (3-O-methylglucose influx), transport plus phosphorylation (2-deoxyglucose uptake), hexokinase, pyruvate dehydrogenase and glucose-6-phosphate dehydrogenase activities were determined in an attempt to localize the metabolic defects. Insulin stimulates 3-O-methylglucose influx 5-fold in normal cells and 3-fold in cells of fasted rats. The basal influx in cells of fasted rats is increased and even more so in cells of hypophysectomized rats where the rate of basal influx is the same as that in cells of normal rats under maximal insulin stimulation. It cannot be further stimulated by insulin. In contrast to 3-O-methylglucose influx, basal uptake and phosphorylation of 2-deoxyglucose in cells of fasted and hypophysectomized rats is drastically decreased and stimulation by insulin is abolished. Total hexokinase and pyruvate dehydrogenase activities are drastically reduced in the homogenate of fat cells of hypophysectomized and fasted rats. Phosphorylation by hexokinase appears to become one of the rate-limiting steps of glucose metabolism in cells of hypophysectomized rats.

3-O-Methylglucose↗
PubMed1986

Insulin-like growth factors/somatomedins: structure, secretion, biological actions and physiological role.

Insulin-like growth factors (IGFs, somatomedins) are structural homologues of insulin with insulin-like biological activity. They are mainly synthesized and secreted by the liver, but may also be produced by extrahepatic tissues. In their native from in blood they are bound to specific carrier protein(s). This determines essentially their biological actions. The complexed factors stimulate growth indices in vitro and in vivo, but, in contrast to the free factors, do not exert acute effects on insulin target tissues.

Animals↗
PubMed1986

Pathophysiological and clinical aspects of the insulin-like growth factors.

Except in acromegaly, where insulin-like growth factor I (IGF I) levels are elevated, only decreased IGF levels have been observed under pathophysiological conditions. These are hypopituitarism, Laron dwarfism, leprechaunism, liver disease, primary hypothyroidism, extrapancreatic tumor hypoglycemia and severe insulin deficiency in experimental animals. For most of these diseases the diagnostic value of IGF determinations is limited. IGF I determinations may serve as a useful additional diagnostic index in acromegaly and in the evaluation of successful operative and/or radiotherapy of this disease.

Acromegaly↗
PubMed1986

Acute metabolic effects and half-lives of intravenously administered insulinlike growth factors I and II in normal and hypophysectomized rats.

Insulinlike growth factors (IGF) act qualitatively like insulin on insulin target tissues in vitro. In the circulation in vivo they are bound to specific carrier proteins. In this form or when continuously infused into hypophysectomized (hypox) rats they do not exert acute insulinlike effects on glucose homeostasis. This study definitively shows that intravenous bolus injections of pure IGF I or II act acutely on glucose homeostasis: they lower the blood sugar, enhance the disappearance of U-[14C]glucose from serum and increase its incorporation into diaphragm glycogen in normal and hypox rats in the presence of antiinsulin serum. The same effects were obtained with recombinant human IGF I injected intravenously either with or without antiinsulin serum into normal rats. Free fatty acid levels decreased transiently only in normal animals. Lipid synthesis from glucose in adipose tissue was not stimulated in hypox and barely stimulated in normal rats. The half-life of injected IGF I or II in normal rats (approximately 4 h) is strikingly different from that in hypophysectomized rats (20-30 min) and appears to depend on the growth hormone-induced 150,000-200,000-mol wt IGF carrier protein that is lacking in hypophysectomized rats. 15 min after the bolus serum IGF I and II concentrations were similar to steady state levels during long-term infusion in hypox rats. Free IGF was barely detectable, however, in the infused animals, whereas 40-100% was found free 15 min after the bolus. These observations for the first time confirm the hypothesis that only free IGF, but not the IGF carrier protein complex, is bioavailable to insulin target tissues.

Animals↗
PubMed1986

Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life.

Adult↗
PubMed1986

Triiodothyronine increases responsiveness of cultured rat bone cells to parathyroid hormone.

Osteoblast-like cells prepared from calvaria of newborn rats and grown in culture for 1 week show markedly increased ornithine decarboxylase (ODC) activity upon exposure to parathyroid hormone (PTH) for 4 h. Triiodothyronine (T3) increases ODC activity of the cultures in long-term experiments but does not stimulate cell replication. Moreover, PTH responsiveness is enhanced by T3. Thus, T3 acts directly on bone cells, and the clinical observation of bone sensitization to PTH by thyroid hormones is confirmed at the cellular level.

Animals↗
PubMed1985

[Prolactin producing hypophyseal adenoma: diagnosis and therapeutic possibilities].

The introduction of radioimmunoassay for prolactin concentrated interest in infertility research on prolactin-producing pituitary adenomas (prolactinomas). In women in the fertile age group these tumors cause amenorrhea and galactorrhea, and in men loss of libido, impotence and occasionally gynecomastia. Microprolactinomas (diameter 10 mm and less) and macroprolactinomas (diameter more than 10 mm) differ in growth characteristics, symptomatology and prognosis. Different therapeutic approaches may be used. Both bromocriptine treatment and selective microsurgical tumor extirpation are successful. Both have advantages and disadvantages, thus rendering the decision as to appropriate treatment increasingly difficult. Recent findings demonstrate that bromocriptine may cause irreversible tumor fibrosis, which decreases the chances of prolactin normalization by subsequent surgery.

Adenoma↗
PubMed1985

In vivo effects of the insulin-like growth factors (IGFs) in the hypophysectomized rat: comparison with human growth hormone and the possible role of the specific IGF carrier proteins.

Insulin-like growth factors (IGF) I and II produce acute insulin-like effects or promote growth indices in hypophysectomized rats, depending on their mode of administration. Intravenous bolus injections of IGF I and II, like insulin, lower the blood sugar level and lead to a pronounced stimulation of glycogen synthesis in skeletal muscle. The two factors are equipotent in this respect. Continuous subcutaneous infusions of IGF I or II over six days have no hypoglycaemic effect. They mimic the effects of growth hormone, increasing the width of the tibial epiphysis and stimulating the thymidine-incorporating activity of costal cartilage in the absence of growth hormone. IGF I (identical to somatomedin C) is more potent than IGF II and causes a dose-dependent increase in body weight at concentrations where IGF II is still ineffective. The absence of acute insulin-like effects in long-term experiments is explained by the presence in serum of highly specific carrier proteins that interfere with the insulin-like properties of IGF I and II and restrict their capillary permeability. Growth hormone induces the formation of both IGF and the major IGF carrier protein in the liver. Thus, while IGFs mediate the actions of growth hormone on growth, growth hormone appears to modulate these actions via IGF carrier proteins.

Animals↗
PubMed1985

Insulin-like growth factors and insulin: comparative aspects.

IGF I and IGF II are two insulin-like growth factors resembling insulin in many respects. They stem from a common precursor, act through receptors similar to the insulin receptor with which they cross-react. When administered in large amounts they produce hypoglycemia. Their major effects, however, are on replication and differentiation of cells of mesodermal origin. IGF I is the major growth promoting factor in vivo. The synthesis and secretion of IGF I by the liver depend on the growth hormone status, insulin and nutrition. In contrast to insulin, the IGFs circulate in blood bound to the carrier proteins. Their half-life in man is in the order of 16 h. IGF I deficiency results in dwarfism (pygmy, Laron dwarf, toy poodle) despite normal or elevated growth hormone secretion. The anabolic actions of insulin and of the IGFs appear to complement each other as shown in Figure 7.

Animals↗
PubMed1985

Insulin-like growth factor I and growth hormone in canine starvation.

The roles of plasma insulin-like growth factor I (IGF I) and growth hormone (GH) were studied in 7 beagle dogs before and during starvation and during refeeding. IGF I levels significantly decreased from 75.2 +/- 5.9 ng/ml at 7 days prior to the start of starvation to 9 +/- 1.7 ng/ml at 19 days after the commencement of starvation (mean +/- SEM; P less than 0.0001). During refeeding IGF I significantly rose from 9 +/- 1.7 ng/ml to 55.5 +/- 7.5 ng/ml within 9 days (mean +/- SEM; P less than 0.002). During starvation plasma GH levels significantly increased (P less than 0.05) and these elevated levels returned to normal during refeeding. The dogs' GH secretory capacity significantly increased during starvation (P = 0.012) and became normal again during refeeding. The following conclusions can be drawn from this study: 1) starvation in the dog leads to a significant and drastic reduction of the circulating levels of IGF I, and 2) starvation in the dog, as in man, leads to increased circulating GH levels and to an increased GH-secretory capacity possibly brought about by a lack of a negative feedback normally exerted by IGF I.

Animals↗
PubMed1985

Comparison of in vivo effects of insulin-like growth factors I and II and of growth hormone in hypophysectomized rats.

Pure human IGF I (43 and 103 micrograms/day) and IGF II (131 micrograms/day) were infused into hypophysectomized rats during 6 days by means of sc implanted minipumps. Their effects on several growth indices were compared with those of various doses of sc infused human growth hormone. Growth hormone infusion produced a dose-dependent rise of endogenous rat IGF from 39 (without growth hormone) to 86 microU equivalents/ml (with 400 mU hGH/day) as determined by a competitive protein binding assay with a human IGF standard. In rats receiving the two doses of IGF I, total serum IGF levels rose to 83 and 99 microU equivalents/ml, respectively, in those receiving the IGF II dose the total serum IGF level rose to 146 microU equivalents/ml. These increases corresponded to steady state levels of 168 and 286 ng/ml of immunoreactive insulin-like growth factor (IR-IGF) I and 320 ng/ml of IR-IGF II. IGF I, but not IGF II led to an increase in body weight similar to that induced by the low doses of hGH (12.5 and 25 mU, respectively). The rise of endogenous rat IGF as well as the infused human IGF I and II caused a widening of the tibial epiphysis and an increase of the [3H]thymidine incorporation into costal cartilage. With respect to these two indices IGF II was clearly less potent that IGF I. When expressed in microU equivalents of the protein binding assay, endogenous rat IGF induced by hGH appeared to be relatively more effective than infused human IGF I or II.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of insulin-like growth factors on chick embryo hepatocytes.

Biological effects of insulin-like growth factors (IGF) I and II on primary cultures of chick embryo liver cells have been investigated and compared 1) with the biological effect of insulin and 2) with competitive binding of the three hormones to their respective binding sites. IGF I and II stimulate the incorporation of D[U-14C]-glucose into liver cell glycogen in a time- and dose-dependent manner, but with a 5-10-fold lower potency than insulin. Both IGFs also lead to enhanced incorporation of 5-[3H]uridine and L[U-14C]valine into trichloroacetic acid (TCA) insoluble material and to activation of ornithine decarboxylase activity. Their potency in stimulating RNA synthesis and ornithine decarboxylase activity is comparable to that of insulin. Protein synthesis is maximally stimulated at 3 nM by all three hormones. In the competitive binding studies, IGF I and II are 10-fold less potent than insulin in competing for [125I]insulin binding, but 100-fold more potent than insulin in competing for [125I]IGF I or II binding. These studies show that IGF I and II stimulate the same metabolic indices as insulin in the chick embryo liver. By comparing these biological effects with competitive binding data it appears that IGFs act on glucose metabolism in the chick embryo liver via the insulin receptor, whereas stimulation of growth indices by IGFs and insulin appears to be mediated by their own specific receptors.

Animals↗