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Insulin modulates circulating endothelin-1 levels in humans

H A Wolpert¹, S N Steen, N W Istfan

¹Department of Internal Medicine, Joslin Diabetes Center, New England Deaconess Hospital, Boston, MA.

Metabolism: Clinical and Experimental

|August 1, 1993

Summary

Insulin increases levels of the vasoconstrictor peptide endothelin-1 (ET-1) in obese women, both before and after weight loss. Weight loss reduced basal ET-1 and insulin levels, but blood pressure changes did not correlate with ET-1 reduction.

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Area of Science:

Endocrinology
Vascular Biology
Metabolic Syndrome

Background:

Insulin is known to stimulate endothelin-1 (ET-1) synthesis in vitro.
Obesity-associated hypertension may involve altered ET-1 levels.

Purpose of the Study:

To investigate whether insulin modulates ET-1 levels in vivo.
To determine the role of insulin-modulated ET-1 in obesity-associated hypertension.

Main Methods:

Euglycemic hyperinsulinemic clamps were performed in eight obese women before and after a 10-week protein-sparing diet.
Circulating immunoreactive ET-1 and insulin levels were measured during clamps.
Basal and clamp-induced ET-1 and insulin levels were compared before and after weight loss.

Main Results:

Insulin infusion increased ET-1 levels in vivo, both before and after weight loss.
Weight loss reduced basal ET-1 levels, correlating with reduced fasting insulin.
Decreased blood pressure after weight loss did not correlate with reduced ET-1 levels.

Conclusions:

Insulin modulates circulating ET-1 levels in vivo in obese women.
While weight loss impacts both insulin and ET-1, the reduction in ET-1 does not directly correlate with blood pressure decrease in this context.