Acute, but not long-term intranasal insulin administration elevates blood pressure

Abstract

Insulin acts in the central nervous system to reduce food intake and body weight and improves cognitive functions. After intranasal administration, insulin enters the cerebrospinal fluid compartment and alters brain functions in the absence of substantial absorption into the blood stream. In a recent study in normal weight men, long-term intranasal insulin administration (160 IU/d over 8 weeks) resulted in a distinct reduction of body weight while acute effects were limited to a transient rise in diastolic blood pressure. The present experiments more systematically assessed effects of intranasal insulin on blood pressure in healthy humans. During sessions of 2h each, insulin (20 IU) and placebo were intranasally administered every 10min to 8 healthy men (age, 24.8±0.5yrs; body mass index, 22.6±1.7kg/m2) and blood pressure was measured also every 10min. After 120min, i.e. after a total intranasal dose of 240 IU, insulin induced a rise in diastolic blood pressure of 13.3±4.8% compared to baseline levels (placebo: +2.0±3.3%, p<0.05). There also was a trend towards elevated systolic blood pressure (+9.3±4.6%, p<0.08). Heart rate and plasma glucose levels remained stable. Results suggest that intranasal insulin after first administration acutely elevates blood pressure, which may be mediated via insulin receptors located in the paraventricular nucleus. After long-term administration of intranasal insulin, this effect vanishes, pointing to a gradual activation of counter regulatory mechanisms.