Insulin infusion reduces hepatocyte growth factor in lean humans

Area of Science:

• Endocrinology
• Metabolic Syndrome Research
• Vascular Biology

Background:

• Plasma Hepatocyte Growth Factor (HGF) is elevated in obesity, a condition linked to increased risk of vascular disease, metabolic syndrome, and cancer.
• HGF's role in obesity-related comorbidities necessitates understanding its regulation, particularly the influence of hyperinsulinemia.

Purpose of the Study:

• To investigate whether hyperinsulinemia elevates plasma HGF levels.
• To explore the relationship between HGF and metabolic/anthropometric markers in a diverse BMI range.

Main Methods:

• A hyperinsulinemic euglycemic clamp was performed on 22 participants (BMI 20.6-34.5 kg/m²).
• Plasma HGF was measured at baseline and steady-state during the clamp.
• Correlations between baseline HGF and various metabolic indicators (triglycerides, liver enzymes, adiponectin) were assessed.

Main Results:

• Fasting HGF positively correlated with weight, BMI, waist circumference, triglycerides, and liver enzymes (ALT, GGT).
• Insulin sensitivity and alanine aminotransferase significantly predicted fasting HGF levels.
• Insulin suppressed HGF during the clamp, but this effect was only significant in lean subjects, with a 7% reduction observed.

Conclusions:

• Liver may be a significant source of circulating HGF in lean individuals, indicated by HGF's correlation with hepatic enzymes.
• In obese subjects, adiposity, not elevated insulin, appears to be the primary driver of increased plasma HGF.
• Weight loss is proposed as the most effective strategy to reduce plasma HGF and mitigate associated health risks.