Insulin infusion reduces hepatocyte growth factor in lean humans

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Insulin infusion reduces hepatocyte growth factor in lean humans

author de Courten, B
author de Courten, MP
author Dougherty, S
author Forbes, JM
author Potts, JR
author Considine, RV
Year 2013
citation Metabolism 2013;62(5):647-50
issn 0026-0495
URI http://hdl.handle.net/11187/1534
abstract OBJECTIVE: Plasma Hepatocyte Growth Factor (HGF) is significantly elevated in obesity and may contribute to vascular disease, metabolic syndrome or cancer in obese individuals. The current studies were done to determine if hyperinsulinemia increases plasma HGF. MATERIALS/METHODS: Twenty-two participants (10 women/12 men, BMI 20.6-34.5 kg/m(2), age 18-49 years) underwent a hyperinsulinemic euglycemic clamp with measurement of HGF at baseline and steady state. Relationships between baseline HGF, anthropometrics, triglycerides, liver enzymes, c-reactive protein and adiponectin were also evaluated. RESULTS: Fasting HGF was positively correlated (P<0.050) with weight (r=0.63), BMI (r=0.55), waist circumference (r=0.68), WHR (r=0.48), triglycerides (r=0.44), alanine aminotransferase (r=0.74) and γ-glutamyl transpeptidase (r=0.56), but not c-reactive protein or adiponectin. In stepwise regression, alanine aminotransferase and insulin sensitivity accounted for significant variation in fasting HGF. A significant effect of insulin to suppress HGF during the clamp (P=0.029) was found after adjustment for BMI. HGF was reduced 7% at steady state in the lean subjects only (437.1 ±57.8 vs 405.4±72.0 pg/ml; P=0.030). CONCLUSIONS: The positive correlation of HGF with hepatic enzymes suggests liver may be a significant source of circulating HGF in lean subjects. The strong correlation of plasma HGF with adiposity and the lack of an effect of insulin to increase HGF during the clamp in obese subjects suggest that adiposity, rather than elevated insulin levels, may be the major contributor to plasma HGF in obese subjects. Thus, a reduction in plasma HGF through weight loss is likely the best way to decrease comorbidities mediated by this angiogenic and mitogenic factor. Copyright © 2013 Elsevier Inc. All rights reserved.
sponsorship NHMRC: 1004503, 586655, 367649 Other
publisher WB Saunders
title Insulin infusion reduces hepatocyte growth factor in lean humans
type Journal Article
doi 10.1016/j.metabol.2012.10.013


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