Evidence for the existence in human serum of large molecular weight nonsuppressible insulin‐like activity (NSILA) different from the small molecular weight forms

Zapf, J.; Jagars, G.; Sand, I. Charles; Froesch, E. R.

doi:10.1016/0014-5793(78)80315-9

Cited by 35 publications

(11 citation statements)

References 20 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the past years, we have failed to detect significant amounts of nonsuppressible insulin-like activity in the large molecular weight serum fractions obtained by Sephadex chromatography in 1 M acetic acid, a routine procedure to extract NSILA-S from serum (10,12). However, when we reinvestigated this discrepancy, we found considerable amounts of nonsuppressible insulin-like activity in large molecular weight serum fractions after acidic Sephadex chromatography, provided that lyophilization of the fractions was replaced by ultrafiltration and extensive dialysis against KrebsRinger bicarbonate buffer (30). In accord with earlier observations (7) and with Poffenbarger's work (29) we were unable to dissociate large molecular weight nonsuppressible insulin-like activity into NSILA-S.…”

Section: Discussionsupporting

confidence: 82%

“…In accord with earlier observations (7) and with Poffenbarger's work (29) we were unable to dissociate large molecular weight nonsuppressible insulin-like activity into NSILA-S. Thus, at least two different molecular entities of nonsuppressible insulin-like activity are present in native serum: (a) NSILA-S that is almost completely bound to a specific carrier protein and that can be dissociated under acidic conditions (10,12,15) (the NSILA-Scarrier complex is inactive on rat heart muscle [16] and adipocytes, this paper) and (b) large molecular weight nonsuppressible insulin-like activity that is active on adipose tissue in vitro (29,30). The latter form seems to account mainly for the nonsuppressible insulin-like activity measured in whole serum by the fat pad assay.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein

Zapf¹,

Schoenle²,

Jagars³

et al. 1979

J. Clin. Invest.

Self Cite

177

View full text Add to dashboard Cite

A B S T R A C T 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 ofendogenous insulin-like activity, inhibits the stimulatory effect of NSILA-S, but not of insulin, on 3-0-methylglucose transport and on lipogenesis from [U-14C]glucose in isolated rat fat cells. Concomitantly, it prevents binding of 125I-labeled NSILA-S to the insulin receptor and to the NSILA-Sbinding 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 alfmost exclusively as NSILA-S-carrier complex. Ac-cording 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.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein

Zapf¹,

Schoenle²,

Jagars³

et al. 1979

J. Clin. Invest.

Self Cite

177

View full text Add to dashboard Cite

show abstract

“…Besides IGFBP-3, no other IGFBPs are found in the 150-kD complex (65, 66) (Fig. The ALS is an Nglycosylated protein with a molecular mass of [84][85][86] kD that does not itself bind IGFs or IGFBP-3 (67). The ALS is an Nglycosylated protein with a molecular mass of [84][85][86] kD that does not itself bind IGFs or IGFBP-3 (67).…”

Section: Role Of Igfbps In the Circulationmentioning

confidence: 99%

Physiological role of the insulin-like growth factor binding proteins

Zapf

1995

European Journal of Endocrinology

177

View full text Add to dashboard Cite

The original observation that insulin-like growth factors (IGFs) are present in native serum as hi gh\ x=req-\ 10 to 40 times higher than the IGF-I affinity of the type 1 IGF receptor (6.7 x 108 1/mol (25)), this does not imply that the bioavailability of IGFBP-bound IGF-I to the type 1 IGF receptor is negligible.Nevertheless, one of the original observations was that partly purified IGFBP preparations attenuated or inhibited both acute (26, 27) and long-term effects of IGF (28). It was, therefore, puzzling that some IGFBPs were found to enhance IGF actions in cell cultures (20,21). Typically, stimulation of IGF action by IGFBPs has not been observed in short-term experiments, i.e. within less than 2 h after addition of fGF together with the IGFBP. The stimulatory mechanism requires at least 24 h. Therefore, DNA synthesis has usually been measured to demonstrate enhanced IGF action. Alter-

show abstract

“…Bioassay characterization of growth peptides forms an essential component in characterization (Zapf, 1983). Only through such methods can one ensure that immunologically or receptor-recognized materials are appropriately active.…”

Section: Methods Of Analysesmentioning

confidence: 99%

Animal Growth Regulation

1989

View full text Add to dashboard Cite

Evidence for the existence in human serum of large molecular weight nonsuppressible insulin‐like activity (NSILA) different from the small molecular weight forms

Cited by 35 publications

References 20 publications

Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein

Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein

Physiological role of the insulin-like growth factor binding proteins

Animal Growth Regulation

Contact Info

Product

Resources

About