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Biomedical subjects

J Zapf

Publications and source records attributed to J Zapf.

At least 181 records · Page 10Linked to original sources
PubMed1981

Dwarfism in the pygmy. An isolated deficiency of insulin-like growth factor I.

Insulin-like growth factors (IGFs) I and II, which are present in normal human beings, were measured in serum samples from 11 pygmies from the Central African Republic, 31 controls, and 12 patients with growth hormone deficiency. The mean serum concentration of IGF-I (+/- S.E.M.) was 68.6 +/- 8 ng per milliliter in pygmies, as compared with 193 +/- 10 ng per milliliter in controls (P less than 0.001) and 24 +/- 4 ng per milliliter in patients with growth hormone deficiency (P less than 0.05). Mean serum concentrations of IGF-II in controls, pygmies, and growth hormone-deficient patients were 647 +/- 22, 503 +/- 37, and 252 +/- 29 ng per milliliter, respectively. The serum IGF-I concentration was within the normal range in only one pygmy, whereas IGF-II values were within the normal range in 10 of 11. Pygmies appear to have a major defect in the production of IGF-I.

Adolescent↗
PubMed1981

Effect of trypsin treatment of rat adipocytes on biological effects and binding of insulin and insulin-like growth factors: further evidence for the action of insulin-like growth factors through the insulin receptor.

Trypsin-treatment of isolated rat adipocytes abolishes the metabolic effects not only of insulin, but also of the insulin-like growth factors: in trypsin-treated cells, concentrations of these hormones that are otherwise maximally effective no longer stimulate 3-O-methylglucose transport and lipogenesis or inhibit epinephrine induced lipolysis. Concomitantly, the trypsin-treated adipocytes no longer display specific insulin binding. In contrast, the characteristics of the binding of the insulin-like growth factors are not grossly affected by prior trypsinization of the adipocytes. These findings add further support to the concept that the insulin-like growth factors act on glucose metabolism and antilipolysis via the insulin receptor of the adipocyte.

3-O-Methylglucose↗
PubMed1981

Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia.

Serum levels of immunoreactive insulinlike growth factors (IGF) I and II were determined by a modified IGF I and a new IGF II radioimmunoassay in normal children and adults, and in patients with acromegaly, isolated growth hormone deficiency, and extrapancreatic tumor hypoglycemia. Serum samples were gel filtered by a simple routine procedure at acidic pH to dissociate and separate IGF from the IGF carrier protein. Mean immunoreactive IGF I levels (+/- SD; corrected for crossreactivity of IGF II) were 193 +/- 58 ng/ml in normal adult subjects, 712 +/- 245 ng/ml in acromegalic patients and 24 +/- 14 ng/ml in patients with isolated growth hormone deficiency. The lack of growth hormone alone, irrespective of an otherwise normal hormonal status, appears to be responsible for the drastic decrease of IGF I levels. Oversecretion of growth hormone does not increase the levels of immunoreactive IGF II: mean levels (+/- SD; corrected for crossreactivity of IGF I) in normal and acromegalic subjects are virtually identical (647 +/- 126 and 641 +/- 189 ng/ml, respectively). Apparently, normal growth hormone levels stimulate IGF II production already maximally. However in growth hormone deficiency immunoreactive IGF II is significantly decreased (252 +/- 99 ng/ml). Thus, IGF II, like IGF I, is growth hormone dependent. But in contrast to IGF I, the growth hormone dependence of IGF II seems to become apparent only at subnormal growth hormone levels. In normal children IGF I is age dependent: it is low in newborn cord sera (51 +/- 20 ng/ml) and gradually rises into the adult range with increasing age. At the onset of and during puberty mean IGF I levels lie above prepubertal values. In contrast, IGF II levels in normal children are independent of age and pubertal stage beyond the first year of life, whereas newborns have significantly lower IGF II values. Hypoglycemia resulting from extrapancreatic tumors is not associated with increased immunoreactive IGF I or II levels. IGF I is decreased in most of the sera (mean level +/- SD:56 +/- 39 ng/ml) whereas IGF II lies in the normal range (556 +/- 195 ng/ml).

Acromegaly↗
PubMed1981

In vivo control of insulin-sensitive phosphodiesterase in rat adipocytes by growth hormone and its parallelism to glucose transport.

As shown previously in adipocytes of hypophysectomized (hypox) rats, 3-O-methyl-glucose transport is already maximal in the basal state and insensitive to insulin. It is normalized by prolonged administration of GH to hypox rats. This study shows glucose transport in the presence and absence of phosphodiesterase (PDE) inhibitors in the fat cells of normal and hypox rats. Enhanced glucose transport in insulin-stimulated normal fat cells as well as enhanced glucose transport in adipocytes of hypox rats is inhibited by PDE inhibitors. The low Km phosphodiesterase activity, which is known to be acutely stimulated by insulin in normal adipocytes, is found to be increased in the fat cells of hypox rats, and further stimulation by insulin is not possible. Normalization occurs after GH administration for 4 days. Then, the low Km PDE activity is again low and stimulated in the presence of insulin. The similarity between the behavior of the activity of the glucose carrier system and that of the low Km PDE suggests that both may be dependent on a GH-induced membrane factor which would be acutely inhibited by insulin.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Interactions of insulin-like growth factors I and II and multiplication-stimulating activity with receptors and serum carrier proteins.

Insulin-like growth factors (IGFs) I and II, purified from human plasma, and multiplication-stimulating activity (MSA), purified from media conditioned by the BRL 3A rat liver cell line, are polypeptides with similar biological and biochemical properties. We have compared the interaction of 125I-labeled and unlabeled MSA, IGF-I, and IGF-II with four intact cell or cell membrane preparations previously shown to possess MSA receptors: rat liver plasma membranes, chick embryo fibroblasts, human fibroblasts, and BRL 3A2 cells. In each case, specific binding of 125I-labeled IGF-I and IGF-II was demonstrated. With each 125I-labeled peptide, significant inhibition of binding and parallel dose-response curves were observed with unlabeled IGF-I, IGF-II, and MSA. Striking differences were noted, however, in the relative potencies of the unlabeled peptides as competitive inhibitors of binding. We conclude that the different specificities of binding inhibition reflect a significant heterogeneity among IGF receptors. A similar heterogeneity appears to occur among somatomedin carrier proteins in rat and human sera.

Animals↗
PubMed1979

Receptor binding and effects of insulin and NSILA-S on glucose transport and metabolism in adipocytes from hypophysectomized rats.

Isolated fat cells from normal and hypophysectomized rats have been compared with respect to: 1) binding of insulin and NSILA-S, and 2) effects of these two hormones on glucose transport and metabolism. Although both insulin and NSILA levels were decreased in the serum of hypophysectomized rats, insulin binding was decreased to about 63% of normal, whereas NSILA-S binding remained unchanged. Basal lipogenesis was similar in adipocytes of normal and hypophysectomized rats, but was not stimulated by either insulin or NSILA-S. Similarly, neither of the two hormones stimulated the net gas exchange of "intact" fat pads from hypophysectomized rats. In striking contrast to these findings, 3-O-methylglucose transport in unstimulated fat cells of hypophysectomized rats proceeded at a maximal rate which was not further enhanced by insulin or NSILA-S. These results suggest that the lack of one or several hormones of the pituitary causes one or several enzyme deficiencies responsible for the limited rate of lipogenesis, which otherwise would proceed at a very rapid rate because of unrestrained glucose transport.

Adipose Tissue↗
PubMed1979

Transport and metabolism of fructose in fat cells of normal and hypophysectomized rats.

We have shown earlier that the glucose carrier of fat cells of hypophysectomized rats operates at maximal speed in the basal state and that these cells are insensitive to insulin. Here we characterize fructose transport and metabolism in adipocytes of normal and hypophysectomized rats. 3-O-methylglucose inhibits insulin-stimulated incorporation of [U-14C]fructose into fat cells and has no significant effect on basal fructose metabolism. In contrast, 2-deoxyglucose inhibits both basal and insulin-stimulated fructose incorporation. Insulin enhances fructose incorporation in normal adipocytes only in the absence of 3-O-methylglucose. In hypophysectomized rats, incorporation of glucose and of fructose is decreased and insensitive to insulin. In contrast to the glucose carrier, the specific fructose carrier appears to be insensitive to insulin and to continue to operate with unchanged characteristics after hypophysectomy. Thus, hypophysectomy leads to a specific alteration of the insulin-sensitive glucose carrier, whereas the insulin-insensitive fructose carrier remains unaltered.

Adipose Tissue↗
PubMed1979

Inhibition of the action of nonsuppressible insulin-like activity on isolated rat fat cells by binding to its carrier protein.

Nonsuppressible insulin-like activity extracted and purified from human serum (NSILA-S) mimics all insulin-like effects in vitro and, after injection, in vivo in the presence of excess insulin antibodies. However, there is no evidence that it exerts acute insulin-like effects in its native form in the circulation, where it is almost completely bound to a specific large molecular weight carrier protein. In this paper we show that partially purified NSILA-S-carrier protein, devoid of endogenous insulin-like activity, inhibits the stimulatory effect of NSILA-S, but not of insulin, on 3-0-methylglucose transport and on lipogenesis from [U-(14)C]glucose in isolated rat fat cells. Concomitantly, it prevents binding of (125)I-labeled NSILA-S to the insulin receptor and to the NSILA-S-binding site. The following explanation is, therefore, offered for the absence of acute insulin-like effects of native NSILA-S in vivo: In native serum NSILA-S occurs almost exclusively as NSILA-S-carrier complex. According to recent findings the passage of this complex through blood capillaries is restricted. The present results indicate that, in addition, it is metabolically inactive, or, at least, possesses reduced metabolic activity. The well-known phenomenon that whole serum, nevertheless, exerts pronounced nonsuppressible insulin-like effects on adipose tissue in vitro seems, therefore, to be mainly caused by the presence of a large molecular weight insulin-like protein not identical to the NSILA-S-carrier complex.

Adipose Tissue↗
PubMed1979

Effects of insulin on glucose metabolism and glucose transport in fat cells of hormone-treated hypophysectomized rats: evidence that growth hormone restricts glucose transport.

In earlier studies we have shown that insulin does not stimulate glucose incorporation in adipocytes of hypophysectomized (hypox) rats. Basal glucose incorporation is decreased, although basal 3-O-methylglycose transport is very rapid and cannot be further stimulated by insulin. In this study we treated hypox rats with human GH, ACTH, and T3, alone or in combination, and examined the effects of insulin on glucose incorporation into fat cells and on 3-O-methylglucose transport. The results show that chronic administration of T3 alone to hypox rats partially restores glucose incorporation into fat cells and, in combination with ACTH, completely restores this incorporation. The two hormones have no effect on the glucose carrier system. The transport rate under T3 and ACTH replacement therapy continues to proceed at a maximal rate, so that basal glucose incorporation is high but not further enhanced by insulin. In contrast, administration of human GH to hypox rats does not influence glucose incorporation but has a marked effect on glucose transport. The basal glucose transport rate returns toward normal and again responds to insulin. This suggests 1) that enzyme activities responsible for the lipogenetic capacity of the fat cell are decreased in hypox rats and returned toward normal by the combined T3/ACTH treatment, and 2) that the limitation of glucose transport in the fat cell is controlled by GH. GH seems to induce a change of the glucose-carrier system; it leads to a restriction of glucose transport, which is acutely modulated by insulin.

Adipose Tissue↗
PubMed1979

Non-suppressible insulin-like activity in Laron's syndrome.

Severe growth retardation is found in patients with high levels of growth hormone and low sulphation factor activity or somatomedin. Also non-suppressible insulin-like activity (NSILA-s) has been found to be very low in a patient with this condition as measured by bioassay, protein binding assay and radioimmunoassay and to be below activities found in hypopituitary patients. Partially purified NSILA-s restored the ability of serum to increase sulphation activity although full restitution may still depend on other factors. These findings support the hypothesis that NSILA-s belongs to the family of somatomedin and thus is involved in promoting growth, and that low activity of these growth factors is a primary cause of the growth retardation found in these patients.

Animals↗