Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion

Phillip Lee, Michael D. Jensen, Gavin D. Divertie, Valarie J. Heiling, Harold H. Katz, Cheryl A. Conover

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of several related proteins that bind and modulate the actions of IGFs. The liver is the primary source of IGFBP-1, and insulin is a major regulator of hepatic IGFBP-1 production. We report five sets of investigations that further define the characteristics of hepatic IGFBP-1 response to insulin. In normal subjects, a continuous high-dose insulin infusion caused a rapid decrease in plasma IGFBP-1 concentrations, with a rate of 0.24 ± 0.04 μg/L·min-1 and a t 1 2 of 89 ± 4 minutes. Conversely, a 3-hour somatostatin (SRIF) infusion caused a 4.5-fold increase in plasma IGFBP-1 levels. SRIF plus low-dose insulin infusion (to inhibit break-through insulin secretion) resulted in a plateau in IGFBP-1 concentrations at 5 to 8 hours, with a t 1 2 to achieve steady state of 60 to 75 minutes. Under similar conditions, a stepped increase in plasma glucose level from 5 to 9 mmol/L had no effect on the rate of IGFBP-1 increase in plasma, indicating that an acute increase in glucose concentration within a physiologic range has no independent inhibitory effect on IGFBP-1 production in the presence of a nonsuppressive insulin level. Using SRIF plus sequential graded insulin infusions, the threshold peripheral (=portal) plasma insulin concentration for IGFBP-1 suppression was between 65 and 172 pmol/L. Subjects with insulin-dependent diabetes mellitus (IDDM) showed a similar dose-response pattern, suggesting that insulin regulation of IGFBP-1 may be normal in IDDM. The rapid and sensitive response of IGFBP-1 to insulin is consistent with its postulated role to modulate IGF bioaction in relation to substrate availability. Moreover, measurement of plasma IGFBP-1 concentrations may serve as a useful marker of hepatic insulin sensitivity.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalMetabolism
Volume42
Issue number4
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 1
Insulin
Liver
Type 1 Diabetes Mellitus
Glucose
Somatostatin
Insulin Resistance

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion. / Lee, Phillip; Jensen, Michael D.; Divertie, Gavin D.; Heiling, Valarie J.; Katz, Harold H.; Conover, Cheryl A.

In: Metabolism, Vol. 42, No. 4, 1993, p. 409-414.

Research output: Contribution to journalArticle

Lee, Phillip ; Jensen, Michael D. ; Divertie, Gavin D. ; Heiling, Valarie J. ; Katz, Harold H. ; Conover, Cheryl A. / Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion. In: Metabolism. 1993 ; Vol. 42, No. 4. pp. 409-414.
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