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Effects of insulin on renal function, sympathetic nervous activity and forearm blood flow in normal human subjects
1Department of Medicine, Toronto Hospital, Ont. florence.wong@utoronto.ca
Objective:
To assess fully the vasodilatory and sodium-retaining effects of insulin.
Design:
Prospective physiologic study using a dose-response protocol.
Setting:
Clinical investigation unit of a tertiary referral hospital.
Participants:
Six normal, healthy men.
Interventions:
Subjects were given increasing doses of insulin intravenously from 10 to 1200 mU/m2 per minute, using the euglycemic "clamp" technique.
Outcome Measures:
Urinary sodium excretion, systemic and renal hemodynamics, plasma norepinephrine levels and forearm blood flow after each dose.
Results:
Low doses of insulin (up to 20 mU/m2 per minute) produced a significant antinatriuresis (0.18 [SEM 0.05] v. 0.37 mmol per minute at baseline, p < 0.01) and antidiuresis (2.53 [SEM 0.67] v. 6.21 [SEM 1.66] mL per minute, p < 0.01) with no associated changes in renal hemodynamics or sympathetic nervous activity. Subsequent higher doses of insulin improved urinary volume and sodium excretion to above baseline levels associated with renal and forearm vasodilatation, although mean arterial pressure remained unaltered.
Conclusions:
Hyperinsulinemia initially causes an antinatriuresis and antidiuresis through a direct action on the renal tubule. The subsequent phenomenon of escape from renal sodium retention may serve as a regulatory mechanism on sodium homeostasis in conditions associated with hyperinsulinemia and sodium retention.