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Postoperative induction of insulin-like growth factor binding protein-3 proteolytic activity: relation to insulin and insulin sensitivity
Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
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1998 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 83, no 7, p. 2509-2515Article in journal (Refereed) Published
Abstract [en]

Increased serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolytic activity (IGFBP-3-PA) has been demonstrated in a number of clinical states of insulin resistance, including severe illness, after surgery, and in noninsulin-dependent diabetes mellitus. In the present study we assessed the role of insulin sensitivity in expression of IGFBP-3-PA in serum. In 18 patients studied, a significant increase in IGFBP-3-PA (P < 0.005) was demonstrated after cole-rectal surgery. Eight patients receiving an oral glucose load before surgery demonstrated a significant greater relative increase in IGFBP-3-PA compared with 10 patients not receiving glucose (32.9 +/- 7.1% vs. 8.6 +/- 6.7%, respectively; P < 0.05). Both groups had reduced insulin sensitivity after surgery(-58 +/- 4%; P < 0.0001; n = 18), as determined by hyperinsulinemic, normoglycemic clamps; however, the group not receiving glucose displayed 18% less insulin sensitivity than the oral glucose load group (P < 0.05). Multiple regression analysis demonstrated that the relative changes in IGFBP-3-PA and C peptide levels were inversely correlated (P < 0.05), suggesting that increased IGFBP-3-PA, presumably increasing IGF bioavailability, may be associated with decreased insulin demands. Interestingly, insulin infusion during the 4-h hyperinsulinemic, normoglycemic clamp performed 24 h after surgery (post-op) resulted in a further increase in IGFBP-3-PA in both groups (P < 0.005), whereas no significant responses could be demonstrated during the pre-op clamp. The expression of increased IGFBP-3-PA was accompanied by conversion of endogenous intact 39/42-kDa IGFBP-3 into its 30-kDa fragmented form as determined by Western immunoblotting, and this conversion was virtually complete after the 4-h post-op clamp in patients displaying marked increases in IGFBP-3-PA. Characterization of the IGFBP-3-PA demonstrated that it was specific for IGFBP-3, as no degradation of IGFBP-1 and -2 was detected, and the use of various protease inhibitors demonstrated that serine proteases and possibly matrix metalloproteinases contribute to the increased IGFBP-3-PA level after surgery. We propose that IGF bioavailability may be increased by the induction of IGFBP-3-PA in insulin-resistant subjects, and that insulin regulates IGFBP-3-PA in this state.

Place, publisher, year, edition, pages
Cary, NC, USA: Oxford University Press, 1998. Vol. 83, no 7, p. 2509-2515
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Medical and Health Sciences Endocrinology and Diabetes
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URN: urn:nbn:se:oru:diva-63892DOI: 10.1210/jc.83.7.2509ISI: 000074562200050PubMedID: 9661636Scopus ID: 2-s2.0-0031728428OAI: oai:DiVA.org:oru-63892DiVA, id: diva2:1171090
Available from: 2018-01-05 Created: 2018-01-05 Last updated: 2018-02-09Bibliographically approved

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Ljungqvist, Olle

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