Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion.
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 microgram/L.min-1 and a t1/2 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 t1/2 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
P D
PD
Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Jensen
M D
MD
Divertie
G D
GD
Heiling
V J
VJ
Katz
H H
HH
Conover
C A
CA
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018970:Insulin-Like Growth Factor Binding Protein 1; D007700:Kinetics; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013004:Somatostatin