title: Is insulin the new intermittent hypoxia?
abstract: The sympathoexcitatory effects of insulin are well-established, although the exact mechanisms by which insulin stimulates the sympathetic nervous system are not completely understood. The majority of research supports a primary role for the central nervous system in the gradual and sustained rise in muscle sympathetic nerve activity (MSNA) in response to hyperinsulinemia; in addition, recent studies in animals suggests carotid body chemoreceptors respond to increases in systemic insulin levels. Intermittent activation of the carotid chemoreceptors, similar to that seen in patients with sleep apnea, can result in sensory long term facilitation and may contribute to the observed rise in baseline MSNA in this population. Consistent with this idea, insulin exposure results in sustained increases in MSNA that persist even when plasma insulin levels return to baseline. We propose the carotid chemoreceptors contribute to insulin-mediated sympathoexcitation and the persistent rise in MSNA in patients with sustained hyperinsulinemia. If the carotid chemoreceptors sense and respond to changes in systemic insulin levels, these organs may provide a viable target for the treatment of disorders known to exhibit sustained hyperinsulinemia and sympathoexcitation including, but not limited to, obesity, hypertension, sleep apnea, metabolic syndrome, cardiovascular disease, and diabetes.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Limberg
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Curry
authors.affiliation: Institute for Integrative Physiology and The Center for Systems Biology of Oxygen Sensing, Biological Science Division, University of Chicago, Chicago, IL 60637, United States.
authors.forename: Nanduri R
authors.initials: NR
authors.lastname: Prabhakar
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States. Electronic address: joyner.michael@mayo.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D002344:Carotid Body / Q000166:cytology / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008954:Models, Biological; D009132:Muscles / Q000294:innervation; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000502:physiology*
chemical_list: D007328:Insulin