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Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans
U Scherrer1, P Vollenweider, D Randin
1Department of Internal Medicine B, CHUV, Lausanne, Switzerland.
Background:
Physiological hyperinsulinemia in lean human subjects stimulates sympathetic nerve activity and blood flow in skeletal muscle, but the underlying mechanism is unknown. Potential mechanisms include central neural or peripheral actions of insulin. Glucocorticoids may potentially interfere with both such actions and thereby may attenuate sympathoexcitatory and vasodilatory effects of insulin in skeletal muscle.
Methods And Results:
To determine whether insulin-induced sympathetic activation and vasodilation are attenuated by dexamethasone, we measured muscle sympathetic nerve activity and muscle blood flow during euglycemic hyperinsulinemia before and after short-term administration of this pharmacological agent. Insulin concentrations, which normally doubled sympathetic activity and markedly increased blood flow, had no such stimulatory effect after short-term dexamethasone administration. In contrast, responses to two noninsulin sympathetic stimuli, the Valsalva maneuver and immersion of the hand in ice water, and the vasodilatory response to calf vascular occlusion were not altered by dexamethasone.
Conclusions:
These results demonstrate a dramatic impairment of insulin-induced sympathetic activation and vasodilation by dexamethasone in lean, healthy humans. This study suggests that dexamethasone administration to lean subjects may offer an experimental model to examine underlying mechanisms that regulate the interplay between cardiovascular, sympathetic, and metabolic effects of insulin.
Insights
Dexamethasone significantly impairs insulin's ability to increase sympathetic nerve activity and blood flow in lean humans. This finding suggests a potential model for studying insulin's cardiovascular and metabolic interactions.
Area of Science:
- Endocrinology
- Cardiovascular Physiology
- Neuroscience
Background:
- Physiological hyperinsulinemia normally stimulates sympathetic nerve activity and skeletal muscle blood flow in lean humans.
- The precise mechanism for insulin's effects on sympathetic activity and vasodilation remains unclear.
- Glucocorticoids may potentially interfere with central or peripheral insulin actions.
Purpose of the Study:
- To investigate whether dexamethasone attenuates insulin-induced sympathetic activation and vasodilation.
- To explore the role of glucocorticoids in modulating insulin's cardiovascular effects.
Main Methods:
- Muscle sympathetic nerve activity and muscle blood flow were measured during euglycemic hyperinsulinemia.
- Measurements were taken before and after short-term dexamethasone administration.
- Responses to non-insulin sympathetic stimuli and other vasodilatory challenges were assessed.
Main Results:
- Dexamethasone administration abolished the normal increase in sympathetic activity and blood flow induced by insulin.
- Responses to the Valsalva maneuver and cold pressor test remained unaltered.
- Dexamethasone did not affect vasodilation following calf vascular occlusion.
Conclusions:
- Dexamethasone significantly impairs insulin-induced sympathetic activation and vasodilation in lean, healthy individuals.
- This impairment highlights a crucial interaction between glucocorticoids and insulin's cardiovascular effects.
- Dexamethasone administration may serve as a model to study the interplay of insulin's metabolic, sympathetic, and cardiovascular actions.