PubMed Health⌕ Search

Biomedical subjects

E R Froesch

Publications and source records attributed to E R Froesch.

At least 181 records · Page 10Linked to original sources
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

The effect of different extraction procedures on two different molecular weight species of serum NSILA and on the carrier protein of small molecular weight NSILA (NSILA-S).

The influence of Dowex-50 adsorption chromatography on the recovery of two different forms of serum NSILA, large and small mol. wt. NSILA, and on the recovery of the binding protein of the small mol. wt. form was studied and compared with another extraction procedure, gel filtration on Sephadex G-50 in 1 M acetic acid. Partially purified NSILA-S is adsorbed to Dowex-50 at pH 6.8. It can be eluted with 20 mM NH4OH and appears unchanged with regard to its biological activity and molecular weight. Adsorption of 125I-labelled NSILA-S to Dowex-50 does not change its binding characteristics to serum. When serum is chromatographed on Sephedex G-50 in 1 M acetic acid, NSILA is obtained in a large and in a small molecular weight form (NSILA-S). After recombination of the small molecular weight NSILA fraction with the "stripped" serum fraction, which contains large mol. wt. NSILA and a specific carrier protein for NSILA-S, re-chromatography of this mixutre on Sephadex G-50 at neutral pH yields NSILA mostly in the void volume. It adsorbs to Dowex-50. After elution from Dowex, acidic gel filtration on Sephadex G-50 results in an elution pattern which is completely different from that of NSILA-S. Adsorption of serum to Dowex-50 results in a dramatic decrease of the NSILA-S binding activity. It is concluded that Dowex-50 adsorption chromatography of serum 1) inactivates most of the serum NSILA-S binding protein 2) leads to the loss of acid dissociable small mol. wt. NSILA (NSILA-S). Therefore, Dowex-50 adsorption chromatography is not suitable for the subsequent determination or further purification of NSILA-S from whole serum.

Adsorption↗
PubMed1979

Optimal blood sugar control in labile diabetics using a portable open-loop insulin infusion system with a flexible program.

11 labile diabetics were well controlled after 2 days of an i.v., open-loop insulin infusion program consisting of constant, empirically determined, basal infusion rates (mean: 1.1 U/h) and superimposed rectangular one-hour insulin infusions between 2 and 8 U/h during the main meals. The steering unit switches automatically back to the basal infusion rate after one hour. An almost optimal blood sugar profile was already obtained on the third day of the infusion program. We believe that such a flexible, open-loop insulin infusion program would render long-term optimal blood sugar control in "labile" diabetics possible if the technological development ever allows implantation of the infusion pumps.

Adolescent↗
PubMed1978

[Adjustment of unstable diabetics with a simple insulin infusion program].

In view of the importance of knowing exactly how much insulin is required by diabetics who are difficult to control with subcutaneous insulin, an insulin infusion program has been tried in such patients. The apparatus, which was produced by Siemens as a prototype, works according to the following simple and flexible principle: During the day a basal rate of insulin is continuously infused. During the three main meals an additional rectangular insulin infusion is initiated by turning a knob. After an hour the apparatus switches automatically back to the basal ratio. We have used this machine in 13 patients who are fully mobile. 11 of them showed an almost ideal blood sugar profile after 4 days. After switching back to subcutaneous insulin 8 of these 11 patients did better than before but not as well as on the insulin infusion program.

Blood Glucose↗
PubMed1978

NSILA-carrier protein abolishes the action of nonsuppressible insulin-like activity (NSILA-S) on perfused rat heart.

Human serum in a concentration of 10% in the perfusion medium failed to increase glucose uptake by the isolated perfused rat heart, indicating that nonsuppressible insulin-like activity (NSILA) in whole serum was inactive in this system. When NSILA-carrier protein was added to partially purified NSILA-S, its biological activity on the rat heart disappeared. In contrast, the action of insulin was not affected by the presence of NSILA-carrier protein. Binding of 125I-labelled NSILA-S to rat heart was inhibited by NSILA-carrier protein. 125I-labelled insulin binding was not inhibited. These results support the hypothesis that NSILA-S bound to serum carrier protein is a large molecular compound which does not readily diffuse out of the capillary bed and therefore does not exert insulin-like effects in vivo.

Animals↗
PubMed1977

Effects of insulin and NSILA on adipocytes of normal and diabetic rats: receptor binding, glucose transport and glucose metabolism.

Isolated fat cells from normal and streptozotocin-diabetic rats were compared with respect to metabolic indices (glucose-uptake, 3-0-methyl-glucose efflux) with and without stimulation by insulin and nonsuppressible insulin-like activity (NSI-LA). In addition, binding studies were carried out with these two hormones. Basal 14C-glucose oxidation and incorporation into lipids was decreased in diabetic cells and their response to insulin and NSILA was greatly reduced. Basal efflux of 3-0-methylglucose from diabetic cells was somewhat faster than from normal cells. The response to insulin and NSILA was less than in normal cells and it was delayed. The apparent number of insulin binding sites as well as their affinity for insulin was increased in diabetic cells. In contrast, the apparent number of binding sites for NSILA was decreased in diabetic cells and their affinity for NSILA was increased. In normal cells insulin enhanced binding of 125I-NSILA more markedly than in diabetic cells. These findings show that the rate-limiting step of impaired glucose metabolism (oxidation and lipogenesis) in diabetic fat cells is beyond the interaction of the hormone with the receptor. They suggest that the apparent number of hormone receptors (insulin, NSILA) on the cell membrane is regulated individually for each binding site.

Adipose Tissue↗
PubMed1977

Demonstration of a specific serum carrier protein of nonsuppressible insulin-like activity in vivo.

The fate of nonsuppressible insulin-like activity (NSILA-S) was studied by injecting a tracer of 125I-NSILA-S iv into rats. Ten minutes after injection of 125I-NSILA-S alone, 20% of the label is found in serum, whereas after the injection of 125-I-insulin or 125I-NSILA-S together with an excess of cold NSILA-S only 8% of the label are recovered. Sephadex G-200 chromatography at neutral pH of serum after injection of 125I-NSILA-S reveals 2 peaks of radioactivity in the high molecular weight region at 67 and 47% bed volume. Five minutes after injection the peak at 67% starts to disappear, whereas the one at 47% persists with a half-life of 3 h. The latter peak was submitted to Sephadex G-200 chromatography at acidic pH which dissociates NSILA-S from its binding protein. The labeled material obtained by this procedure still exhibits the same binding characteristics to chick embryo fibroblasts as standard 125 I-NSILA-S. A third peak at 90% bed volume corresponding to low molecular NSILA-S is no longer detectable 20 min after injection. A fourth peak at 100% bed volume becomes apparent after 1 h. The half-life and chromatographic pattern of iv injected 125 I-NSILA-S are not changed by the simultaneous administration of insulin or growth hormone. These findings confirm the existence of a specific serum carrier protein for NSILA-S and may explain why endogenous NSILA-S does not exert insulin-like effects under physiological conditions in vivo.

Animals↗
PubMed1977

Non-suppressible insulin-like activity during acute metabolic and endocrine changes in dogs.

Non-suppressible insulin-like activity (NSILA-S) was determined in dogs after acute changes in the blood sugar and after injection of growth hormone. Serum was chromatographed over Sephadex G-50 columns equilibrated in 1 M acetic acid and NSILA-S was determined in the fractions between 55 and 85% column volume using a protein binding assay and the conventional fat pad assay. The results obtained with these two methods correlated rather well (r = 0.74). Hyperglycaemia induced by an intravenous glucose load, by intravenous administration of mannoheptulose or both was not followed by an increase in NSILA-S levels. The injection of insulin and human growth hormone did not lead to alterations of the NSILA-S levels. It is concluded that total NSILA-S levels in the dog do not change acutely following manipulations of the blood sugar and that, in all likelihood, NSILA-S plays no role in the regulation of blood glucose.

Animals↗