Biomedical subjects

A Skottner

Publications and source records attributed to A Skottner.

At least 37 records · Page 2Linked to original sources

PubMed1994

Effects of insulin-like growth factor-I (IGF-I), insulin and combined IGF-I-insulin infusions on protein metabolism in dogs.

The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min-1 kg-1), insulin (3.4, 10.3 or 68.8 pmol min-1 kg-1) or combined infusions (34 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin or 103 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin) on protein metabolism, using an infusion of [1-14C]leucine was investigated in anaesthetized fasted dogs. Leucine concentration, production rate (measure of protein degradation), oxidation rate and non-oxidative disappearance rate (measure of protein synthesis) were decreased in a similar dose dependent manner by the IGF-I and insulin infusions (P < 0.01). The decrease in these measurements of leucine metabolism were greater following 34 pmol IGF-I + 3.4 pmol insulin than with either component infused alone (P < 0.05). Free fatty acid concentrations were decreased by all insulin doses (P < 0.01) but only by 103 and 688 pmol min-1 kg-1 insulin-like growth factor (P < 0.05, P < 0.01). These data demonstrate that IGF-I, like insulin, has a dose dependent effect on protein metabolism and that combined insulin and IGF-I infusions have additive effects on protein metabolism.

Animals↗

PubMed1994

Recombinant human insulin-like growth factor 1 (rh-IGF-1) stimulates erythropoiesis in adult, but not in newborn mice.

The in vivo effect of recombinant human insulin-like growth factor (rh-IGF-1) upon erythropoiesis was studied in inbred BALB/C mice. Unweaned, rapidly growing 20 days old mice and adult female mice received subcutaneous rh-IGF-1 or control injections every 6 h for 48 h. The mice were killed either 12 or 48 h after the last injection, i.e. a study time of 60 and 96 h, respectively. Bone marrow erythroid colony forming units (CFU-E), reticulocytes, haematocrit, serum immunoreactive erythropoietin (siEPO) and body and organ weight were measured. An additional group of young mice were given iron prior to the rh-IGF-1 injections to ensure sufficient available iron. No differences in overall body or organ weights were observed. In the young mice erythropoiesis as measured by bone marrow CFU-E, reticulocytes and haematocrit did not differ between rh-IGF-1 group and controls. When iron alone was given, reticulocytes (P < 0.05) and haematocrit (P < 0.0001) increased significantly, but no further stimulation was seen when rh-IGF-1 injections were given in addition to iron. The adult female mice responded with significantly increased erythropoiesis as judged by increased reticulocyte counts following rh-IGF-1 injections (P < 0.001). No significant effect upon CFU-E and haematocrit was detected. The reticulocyte response was more pronounced at 96 than at 60 h after the first rh-IGF-1 injection. SiEPO was significantly (P < 0.01) lower in the adult 96 h rh-IGF-1 group than in the appropriate control group. In conclusion parenteral iron significantly increased haematocrit in unweaned mice. Short time rh-IGF-1 treatment did not stimulate erythropoiesis in these rapidly growing mice, whether or not iron supplementation had been given.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1994

Insulin-like growth factor-I and insulin have no differential effects on glucose production and utilization under conditions of hyperglycemia.

We have previously shown that in moderately hyperglycemic depancreatized dogs, a glucose-lowering infusion of insulin-like growth factor-I (IGF-I) increased glucose utilization and lactate more, and suppressed glucose production and lipolysis less, than an equipotent glucose-lowering dose of insulin. Similar differences have been observed by others in nondiabetic and diabetic rats. To determine whether the decline in glycemia was important in detecting differential effects of IGF-I and insulin on glucose turnover, IGF-I (0.43 micrograms/kg.min; n = 6) or insulin (0.9 mU/kg.min; n = 9) were infused for 180 min, while hyperglycemia (approximately 180 mg/dl) was maintained. The decline of plasma glucose specific activity was minimized by using the matched step tracer infusion ([6-3H]- and [2-3H]glucose) method. Our results confirmed the approximately 10% potency of IGF-I on glucose metabolism compared to insulin and the lack of effect of IGF-I on insulin clearance. Under conditions of hyperglycemia, the glucose turnover findings were unexpected; there was no difference in the inhibition of glucose production (difference from basal, 2.7 +/- 0.4 mg/kg.min with IGF-I and 2.4 +/- 0.2 with insulin) or the stimulation of glucose utilization (difference from basal, 4.5 +/- 0.8 mg/kg.min with IGF-I and 4.7 +/- 1.3 with insulin). However, lactate increased more (P < 0.01) with IGF-I (from 1230 +/- 163 to a peak of 1903 +/- 349 microM) than insulin (from 1209 +/- 291 to 1535 +/- 340 microM) despite the same increment in glucose utilization. FFA and glycerol declined more with insulin, but the difference was not significant. IGF-I and insulin suppressed plasma amino acids to an equivalent extent. We concluded that 1) the differential effects of IGF-I and insulin on glucose turnover are masked under conditions of hyperglycemia; and 2) because insulin and IGF-I induced the same increment in glucose utilization, but lactate increased more with IGF-I, IGF-I might affect intracellular glucose metabolism differently from insulin. The failure of IGF-I to induce greater glucose utilization than insulin during hyperglycemia, the greater rise in lactate with IGF-I treatment, and the absence of differential effects on proteolysis indicate that IGF-I might have only limited clinical application in the treatment of diabetes.

Animals↗

PubMed1994

Immunohistochemical aspects of insulin-like growth factors I and II in the bovine corpus luteum.

The cellular distribution of insulin-like growth factors I and II (IGF-I and -II) was examined in bovine corpora lutea at different stages of the luteal phase using specific antibodies and the avidin-biotin immunoperoxidase technique. At the cellular level, intense immunostaining for IGF-I was exclusively observed in large and small luteal cells and in a limited number of endothelial cells. Positive IGF-I immunoreactivity in luteal cells was thereby distributed in a distinct topographical, lobule-specific manner. Immunoreactivity in central areas of luteal lobules was most abundant in large luteal cells, whereas in peripheral zones significantly (P < 0.05) more small luteal cells exhibited IGF-I immunoreactivity. This distribution pattern was evident from day 4 of the cycle onwards and occurred at all the stages investigated. The percentage of positive small (SLC) and large (LLC) luteal cells revealed by semiquantitative analysis depended on the stage of the cycle as follows: days 4-7: 34% LLC versus 21.3% SLC in central areas and 25.1% LLC versus 32.7% SLC in peripheral zones; days 8-12: 42.9% LLC versus 19.9% SLC in central areas and 23.5% LLC versus 35.2% SLC in peripheral zones; days 13-16: 47.7% LLC versus 19.4% SLC in central areas and 19.2% LLC versus 41.4% SLC in peripheral zones. In contrast to IGF-I, no expression of IGF-II immunoreactivity was seen in large or small luteal cells. Positive immunoreactivity was restricted to the perivascular fibroblasts of large blood vessels and to the pericytes of capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of insulin-like growth factor-I (IGF-I) and IGF-II on the growth of antler cells in vitro.

The effects of insulin-like growth factors -I and -II (IGF-I and -II) on the growth of undifferentiated (fibroblast zone) cells from the growing tip of red deer velvet antlers and from cells 1.5 cm distal to the growing tip (cartilage zone) were investigated in primary cell culture. The addition of IGF-I or IGF-II to the medium of cultures preincubated in serum-free medium for 24 h increased the rate of [3H]thymidine uptake in a dose-dependent manner in both cell types, with maximal stimulation occurring when 1 nM-30 nM was added. The addition of IGF-II to the incubation medium containing IGF-I did not cause a further increase in [3H]thymidine uptake in either cell type over and above each growth factor alone, indicating that there were unlikely to be synergistic effects of IGF-II on the mitogenicity of IGF-I. Binding studies were carried out using 3 x 10(5) fibroblast zone cells and cartilage zone cells after they had been incubated in serum-free medium for 24 h. 125I-Labelled IGF-I (10(-9) M) in a final volume of 200 microliters was added to each culture and incubation carried out at 4 degrees C for a further hour. 125I-Labelled IGF-I bound specifically to both fibroblasts and cartilage zone cells; binding was displaced by both unlabelled IGF-I and by IGF-I antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Comparative studies of the granulopoietic enhancing effects of biosynthetic human insulin-like growth factors I and II.

The effect of biosynthetic human insulin-like growth factor I (IGF-I) and IGF-II on the in vitro growth of human marrow myeloid progenitors in the presence of recombinant human granulocyte colony stimulating factor (rhG-CSF), granulocyte-macrophage CSF (rhGM-CSF), or interleukin-3 (rhIL-3), was investigated. IGF-I and IGF-II similarly enhanced the growth of myeloid progenitors in cultures stimulated with any of the above hemopoietic regulators. Analysis of colony composition showed an increase in the numbers of granulocyte colonies, but no alteration in the numbers of macrophage or granulocyte/macrophage colonies. IGF-I induced an increase of 62 +/- 16%, 84 +/- 13%, and 107 +/- 18% in granulocyte colony numbers in the presence of G-CSF, GM-CSF, or IL-3, respectively. The values for IGF-II were 66 +/- 13%, 96 +/- 12%, and 91 +/- 12%. Similar enhancement of myeloid colony formation by both peptides was also detected in G-CSF and GM-CSF-stimulated cultures of marrow cells that had been depleted of accessory cells, while neither peptide exerted any effect in the presence of IL-3 in such cultures. The growth-promoting effects of IGF-I and IGF-II were completely abrogated by monoclonal antibodies directed against the IGF-I (Type I) membrane receptor. IGF-I and IGF-II thus appear to exert their effects on human marrow myeloid progenitors via a direct mechanism involving the Type I receptor.

Antibodies↗

PubMed1993

In-vitro response of erythroid progenitors from children with thalassaemia major to human growth hormone and insulin-like growth factor I.

OBJECTIVE: Most short-statured children with beta-thalassaemia major have markedly reduced levels of circulating insulin-like growth factor I (IGF-I). Both human growth hormone (hGH) and IGF-I enhance the in-vitro growth of erythroid progenitors, with hGH exerting its effects via paracrine production of IGF-I. The aim of this study was to characterize further the hGH-IGF-I axis abnormalities in thalassaemia major by evaluating the erythroid potentiating effects of both peptides in cultures of thalassaemic and control erythroid progenitors. DESIGN: Ten short-statured thalassaemic children and nine age-matched healthy donors were evaluated for the in-vitro response of their peripheral blood erythroid progenitors to stimulation with hGH and IGF-I. MEASUREMENTS: The frequency of erythroid progenitors in serum-free cultures of thalassaemic and control peripheral blood mononuclear cells was enumerated following 14 days of incubation in the presence of hGH or IGF-I. RESULTS: Biosynthetic hGH induced a similar dose-dependent magnitude of colony enhancement in cultures of erythroid progenitors from thalassaemic children, as compared to controls. Significant enhancement of colony growth was detected at 42 mU/l hGH, with a maximal effect detected at 83 mU/l of this hormone (173 +/- 8 vs 153 +/- 9% of baseline erythroid progenitors in patients versus controls, respectively). Enhancement of both thalassaemic and control erythroid precursors by hGH was completely abrogated by monoclonal antibodies (alpha IR-3) directed against the IGF-I membrane receptor, thereby confirming the normal capacity of thalassaemic accessory cells to produce IGF-I in response to hGH. Biosynthetic IGF-I also enhanced the growth of thalassaemic and control erythroid precursors to 172 +/- 17 and 159 +/- 10% of baseline at 100 and 10 U/l, respectively. CONCLUSIONS: Our detection of a normal capacity of thalassaemic peripheral blood target cells to response to hGH and IGF-I suggests that these patients do not suffer from a specific defect in receptor and/or post-receptor mechanism(s) involving the response of these cells to both peptides. The normal responsiveness of thalassaemic target cells to hGH and IGF-I suggests that both peptides may be useful in the treatment of growth retardation in thalassaemia.

Adolescent↗

PubMed1992

Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?

The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.

Adult↗

PubMed1992

Comparative studies of the erythroid-potentiating effects of biosynthetic human insulin-like growth factors-I and -II.

The erythroid-potentiating effects of biosynthetic human insulin-like growth factor-I (IGF-I) and IGF-II were evaluated and compared in serum-free cultures of human marrow erythroid progenitors. IGF-I and IGF-II enhanced the in vitro growth of relatively mature (CFU-E) and primitive (BFU-E) erythroid progenitors at similar dose-dependent magnitudes. Significant elevations in erythroid colony counts were detected at 0.2-0.6 ng/mL of both peptides, with a maximal increase in CFU-E and BFU-E numbers detected at 2-6 ng/mL. Similar enhancement of erythroid progenitor cell growth by both peptides was also detected in cultures of marrow cells that had been depleted of accessory cells or in cultures of highly enriched hemopoietic progenitors. IGF-I and IGF-II enhanced erythroid progenitor cell growth at both limiting and saturating concentrations of recombinant human erythropoietin or granulocyte-macrophage colony-stimulating factor, but did not alter the sensitivity of CFU-E and BFU-E to their respective hemopoietic regulators. The erythroid-potentiating effects of IGF-I and IGF-II were completely abrogated by monoclonal antibodies directed against IGF-I membrane receptors. IGF-I and IGF-II thus appear to exert their effects on human marrow erythroid progenitors via a direct mechanism involving the type I IGF receptor.

Antibodies, Monoclonal↗

PubMed1992

In-vivo regulation of messenger RNA encoding insulin-like growth factor-I (IGF-I) and its receptor by diabetes, insulin and IGF-I in rat muscle.

The effects of continuous or acute administration of insulin or insulin-like growth factor-I (IGF-I) on IGF-I mRNA and IGF-I receptor mRNA were studied in the skeletal muscle (gastrocnemius), heart muscle and vascular smooth muscle (aorta) of non-diabetic and diabetic rats using a solution hybridization assay. The levels of IGF-I mRNA in the different types of muscle markedly decreased by diabetes, whereas changes in IGF-I receptor mRNA were less consistent. Continuous infusion of diabetic rats with insulin (28 or 35 nmol/day) for 4 days normalized the altered levels of IGF-I mRNA and IGF-1 receptor mRNA. Infusion of equimolar concentrations of IGF-I did not affect IGF-I mRNA, but decreased the level of IGF-I receptor mRNA in skeletal muscle. In acute experiments, rats were injected with equipotent blood glucose-lowering doses of insulin (14 nmol) or IGF-I (107 nmol). Insulin did not significantly affect levels of IGF-I mRNA, but decreased levels of IGF-I receptor mRNA in skeletal muscle and aorta. IGF-I increased levels of IGF-I mRNA in heart muscle, and markedly decreased levels of IGF-I receptor mRNA in skeletal muscle and heart muscle from non-diabetic and diabetic rats. In conclusion, exogenous IGF-I and insulin can increase IGF-I mRNA and decrease IGF-I receptor mRNA, indicating that both insulin and IGF-I can act as regulators of the IGF-I system in muscle in vivo.

Animals↗

PubMed1991

Does insulin-like growth factor I (IGF-1) trigger the cell body reaction in the rat sciatic nerve?

Regeneration was measured after the infliction of a crush lesion on rat sciatic nerves which 4 days earlier had been subjected to a distal conditioning transection. Such nerves exhibited an increased outgrowth of nerve fibers as compared to nerves subjected to a single crush lesion. This increased outgrowth could be prevented, if the nerve was locally perfused around the site of the transection during the 4 days conditioning interval, with cycloheximide, actinomycin D and vinblastine, inhibitors of protein-, RNA-synthesis and retrograde axonal transport, respectively. The inhibitory effect of cycloheximide could be overcome by simultaneous perfusion with insulin-like growth factor I (IGF-1). The results suggest that proteins including IGF-1 which are synthesised locally around a nerve lesion and then transported retrogradely could trigger regenerative events in the neuronal cell body.

Animals↗

PubMed1991

Binding and biological effects of insulin, insulin analogues and insulin-like growth factors in rat aortic smooth muscle cells. Comparison of maximal growth promoting activities.

Binding and growth promoting effects of insulin, insulin analogues modified in the B chain, proinsulin, insulin-like growth factor-I and -II were studied in cultured rat aortic smooth muscle cells. Specific binding of 125I-insulin was 0.9 +/- 0.2% of total 125I-insulin added, and the IC50-value was estimated to 8.9 pmol/l. The insulin analogue B10 Asp tended to be more potent than insulin in displacing 125I-insulin, B28 Asp was equipotent, B9 Asp/B27 Glu was approximately 100 times less potent and insulin-like growth factor-I more than 1000 times less potent than insulin. Specific binding of 125I-insulin-like growth factor-I after 4 h incubation at 10 degrees C was five times higher than the specific binding of insulin (4.4 +/- 0.4% of total 125I-insulin-like growth factor-I added), and the IC50-value was 0.3 nmol/l. Insulin was approximately 500 times less potent than insulin-like growth factor-I in displacing 125I-insulin-like growth factor-I. The insulin analogue B10 Asp was slightly more potent and analogue B28 Asp was equipotent with insulin. Analogue B9 Asp/B27 Glu was ten times less potent and proinsulin was more than ten times less potent than insulin. The order of potency was similar for 3H-thymidine incorporation into DNA: insulin-like growth factor-I greater than B10 Asp greater than insulin-like growth factor-II greater than insulin greater than or equal to B28 Asp greater than B9 Asp/B27 Glu greater than proinsulin. The maximal effect of insulin-like growth factor-I on 3H-thymidine incorporation was 71 +/- 16% higher than the maximal effect of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Metabolic interfaces between growth and reproduction. IV. Chronic pulsatile administration of growth hormone and the timing of puberty in the female sheep.

Puberty in the female lamb is accompanied by an increased frequency of LH pulses, and during normal development this is preceded by a decline in GH. Conversely, in the growth-retarded lamb, when LH levels are depressed by low nutrition, GH secretion is elevated. Based upon this inverse relationship, we tested the hypothesis that GH may act as a metabolic signal from the brain to inhibit the secretion of LH, and that the decline in GH times puberty. Our approach was to extend high circulating GH levels far beyond the early postnatal period, in a physiological pattern and level, in an attempt to block the pubertal LH rise. To evaluate the pattern of LH as a continuous variable under conditions of constant estradiol negative feedback, the gonadotropin was measured in blood samples collected by jugular venipuncture twice weekly; the lambs were ovariectomized and treated chronically with estradiol (Silastic capsule) beginning at 3 weeks of age. Nine lambs served as untreated controls, and 7 were infused iv with pituitary-derived bovine GH (bGH) between 5 and 28 weeks of age. A programmable backpack infusion pump delivered bGH as hourly pulses, with a total dose of 18 micrograms/kg.24 h, to maintain a physiological pattern and level of GH. At various ages, blood samples were collected at 12-min intervals for 6 h to monitor patterns and levels of peripheral LH and GH. Circulating GH in untreated and treated lambs averaged 7.7 +/- 1.5 ng/ml over a 6-h period at 4 weeks of age and declined to 1.1 +/- 0.2 ng/ml by 19 weeks in the untreated lambs; in contrast, bGH-infused lambs averaged 10.4 +/- 0.9 ng/ml at 19 weeks. Although body weights did not differ, back fat depth and quantity of perirenal fat were reduced in bGH-treated females compared to that in controls. Moreover, insulin-like growth factor-I levels were higher in bGH-treated compared with control lambs, and the bGH-treated lambs exhibited glucose intolerance, thus confirming that infused bGH was biologically active. Neuroendocrine sexual maturity, however, was not different in bGH-treated and control lambs, and it occurred at 21-22 weeks of age. The results do not support our hypothesis that decreasing GH secretion is a requirement for puberty in the sheep. Moreover, unlike in children with delayed puberty, exogenous bGH did not advance normal puberty in the lamb.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Indications that branched chain amino acids, in addition to glucagon, affect the glomerular filtration rate after a high protein diet in insulin-dependent diabetes.

Hormonal changes and whole blood free amino acid levels and their relation to renal function were measured in 12 insulin-dependent diabetic patients after two 10-day periods with a diet consisting of 10% and 20% respectively of the energy as protein. The patients were 15-21 years old and mean duration of diabetes was 12 (5-20) years. Glomerular filtration rate, renal plasma flow, and albumin excretion rate were measured together with plasma concentrations of glucagon, growth hormone, insulin-like growth factor 1 (IGF-1), somatostatin, serum insulin and free amino acids in blood. Glomerular filtration rate was 123 +/- 3 ml/min/1.73 m2 on high protein diet and 113 +/- 3 ml/min/1.73 m2 on low protein diet (p = 0.02). Renal plasma flow was unchanged. Glucagon, IGF-1, branch chained amino acids (BCAA), tyrosine, phenylalanine, lysine, and methionine were increased after the high protein diet. Growth hormone, somatostatin, insulin, and other amino acids remained unchanged. The increase in glomerular filtration rate was significantly correlated to the increase in glucagon, isoleucine, and valine (glucagon r = 0.71, p = 0.01, isoleucine r = 0.59, p = 0.04, valine r = 0.62, p = 0.03). In a multiple regression model the increase in glomerular filtration correlated most strongly to the increase in isoleucine, followed by valine and glucagon. Together these variables explained 88% of the total variance of the change in glomerular filtration rate (r2 = 0.88, p = 0.001). Albumin excretion rate was correlated to IGF-1 (r = 0.86, p less than 0.001) on the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Expression of insulin-like growth factor 1 in sarcomas.

The expression of insulin-like growth factor-1 (IGF-1) was studied in normal tissues, in eight benign lesions and in 50 sarcomas. In palmar fibromatosis the spindle cells in cell-dense areas exhibited a strong immunoreactivity. IGF-1 was variably found in leiomyosarcomas (7/8), malignant schwannomas (7/9), synovial sarcomas (2/3), liposarcomas (3/6), fibrosarcomas (1/3), malignant fibrous histiocytomas (10/18) and in one angiosarcoma. Two rhabdomyosarcomas failed to express IGF-1 and only the spindle cell component of synovial sarcomas was positive. Immunoreactivity for IGF-1 in 10 malignant filrous histiocytomas (MFH) appeared to be related to co-expression of smooth muscle actin. These findings imply that MFHs can be subdivided into a group of tumours which are devoid of morphological and immunophenotypic evidence of differentiation and a group which manifest immunophenotypic differentiation.

Actins↗

PubMed1990

Insulin sensitivity and glucose-induced insulin response changes during adolescence.

Recently we reported that insulin resistance and glucose induced insulin release are inversely correlated to age in young healthy siblings of diabetic patients. To confirm this pattern of change with age, the subjects were reexamined after two years. The study was limited to the age groups with the lowest insulin sensitivity, i.e. 14.0-15.9 years for females and 16.0-17.9 years for males. All five girls and four of five boys showed an increased insulin sensitivity as measured by the somatostatin-insulin-glucose infusion test (p = 0.02). All subjects showed a decrease in fasting levels of insulin-like growth factor 1 (IGF-1) (p less than 0.01) during the observation period. All except one showed an increase in the levels of dehydroepiandrosterone sulphate (DHEA-S) (p less than 0.01). These data confirm that insulin sensitivity increases in the late teenage period. The parallelism to the changes of IGF-1 indicate that the pubertal changes in insulin sensitivity may partly be caused by growth hormone. Our data contradict the hypothesis that the low insulin sensitivity of puberty is due to the increased levels of DHEA-S.

Adolescent↗

PubMed1990

Anabolic and tissue repair functions of recombinant insulin-like growth factor I.

Recombinant human insulin-like growth factor I (rhIGF-I) has been produced in yeast and purified using conventional biochemical techniques. It has been shown to have receptor-binding properties and in vitro growth-promoting activities comparable to those of plasma-derived IGF-I. The anabolic actions of IGF-I can be studied using both systemic and local administration in vivo. The growth-promoting activity and systemic anabolic actions of recombinant IGF-I were studied in mutant dwarf rats. IGF-I was infused intravenously for 9 days and resulted in a significant gain in body weight and significant bone growth, though the effects were not as great as those observed with human growth hormone (hGH). IGF-I also had selective effects on specific organs which were not observed in hGH-treated animals. The results indicate that the growth-promoting effects of IGF-I show a different pattern compared to hGH. The effects of local administration of recombinant IGF-I on tissue regeneration and maintenance were also studied in hypophysectomized and normal rats. After hypophysectomy, the regeneration processes were impaired when both peripheral nerve regeneration and incision wound healing were considered. The results indicate that local administration could have significant effects on regeneration of, for example, peripheral nerves.

Animals↗

PubMed1990

Effects of growth hormone on muscle regeneration and IGF-I concentration in old rats.

A study was made of regeneration of skeletal muscle in young adult and old rats and of the effects of administration of growth hormone to old rats. Regeneration was achieved by subjecting the right extensor digitorum longus muscle to ischaemic necrosis. The level of insulin-like growth factor I in serum was markedly decreased in old rats of 27 months of age compared with young adult rats aged 6 months. Daily injections of 4 IE recombinant human growth hormone during the 10 weeks of regeneration increased the level of insulin like growth factor I to almost the same levels as in rats aged 6 months. The body weight increased by 13% in the old rats treated with recombinant human growth hormone, while the weight of the untreated old rats was constant. The regenerating right and the normal left extensor digitorum longus muscles were studied 10 weeks after the ischaemic necrosis. The absolute and relative weights of regenerating muscle were decreased in 27-month-old rats compared with the rats aged 6 months. No significant difference between normal old rats and old rats treated with recombinant human growth hormone was observed either in muscle weight or in maximum contraction force. The results show that old rats have reduced levels of circulating insulin-like growth factor I. Administration of recombinant human growth hormone raises the level of insulin-like growth factor I to that of young adult rats, and causes an increased body weight. Muscle regeneration after ischaemic necrosis is impaired in old rats apparently by the formation of large amounts of connective tissue. Supplementation with growth hormone does not reverse this impairment.

Aging↗