Insulin infusion reduces hepatocyte growth factor in lean humans

Barbora de Courten, Maximilian Pangratius J De Courten, Sonia L Dougherty, Josephine M Forbes, Jenna R Potts, Robert V Considine

Research output: Contribution to journalArticleResearchpeer-review

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/m2, 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.
Original languageEnglish
Pages (from-to)647-650
Number of pages4
JournalMetabolism
Volume62
Issue number5
DOIs
Publication statusPublished - 2013
Externally publishedYes

Cite this

de Courten, Barbora ; De Courten, Maximilian Pangratius J ; Dougherty, Sonia L ; Forbes, Josephine M ; Potts, Jenna R ; Considine, Robert V. / Insulin infusion reduces hepatocyte growth factor in lean humans. In: Metabolism. 2013 ; Vol. 62, No. 5. pp. 647-650.
@article{d3ee4b3834654a77bc2cdd369de81063,
title = "Insulin infusion reduces hepatocyte growth factor in lean humans",
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/m2, 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.",
author = "{de Courten}, Barbora and {De Courten}, {Maximilian Pangratius J} and Dougherty, {Sonia L} and Forbes, {Josephine M} and Potts, {Jenna R} and Considine, {Robert V}",
year = "2013",
doi = "10.1016/j.metabol.2012.10.013",
language = "English",
volume = "62",
pages = "647--650",
journal = "Metabolism",
issn = "0026-0495",
publisher = "Elsevier",
number = "5",

}

Insulin infusion reduces hepatocyte growth factor in lean humans. / de Courten, Barbora; De Courten, Maximilian Pangratius J; Dougherty, Sonia L; Forbes, Josephine M; Potts, Jenna R; Considine, Robert V.

In: Metabolism, Vol. 62, No. 5, 2013, p. 647-650.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Insulin infusion reduces hepatocyte growth factor in lean humans

AU - de Courten, Barbora

AU - De Courten, Maximilian Pangratius J

AU - Dougherty, Sonia L

AU - Forbes, Josephine M

AU - Potts, Jenna R

AU - Considine, Robert V

PY - 2013

Y1 - 2013

N2 - 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/m2, 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.

AB - 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/m2, 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.

UR - http://www.sciencedirect.com/science/article/pii/S0026049512004052

U2 - 10.1016/j.metabol.2012.10.013

DO - 10.1016/j.metabol.2012.10.013

M3 - Article

VL - 62

SP - 647

EP - 650

JO - Metabolism

JF - Metabolism

SN - 0026-0495

IS - 5

ER -