title: Evidence That the Sympathetic Nervous System Elicits Rapid, Coordinated, and Reciprocal Adjustments of Insulin Secretion and Insulin Sensitivity During Cold Exposure.
abstract: Dynamic adjustment of insulin secretion to compensate for changes of insulin sensitivity that result from alteration of nutritional or metabolic status is a fundamental aspect of glucose homeostasis. To investigate the role of the brain in this coupling process, we used cold exposure as an experimental paradigm because the sympathetic nervous system (SNS) helps to coordinate the major shifts of tissue glucose utilization needed to ensure that increased thermogenic needs are met. We found that glucose-induced insulin secretion declined by 50% in rats housed at 5°C for 28 h, and yet, glucose tolerance did not change, owing to a doubling of insulin sensitivity. These potent effects on insulin secretion and sensitivity were fully reversed by returning animals to room temperature (22°C) for 4 h or by intravenous infusion of the α-adrenergic receptor antagonist phentolamine for only 30 min. By comparison, insulin clearance was not affected by cold exposure or phentolamine infusion. These findings offer direct evidence of a key role for the brain, acting via the SNS, in the rapid, highly coordinated, and reciprocal changes of insulin secretion and insulin sensitivity that preserve glucose homeostasis in the setting of cold exposure.
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Muta
authors.affiliation: Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Kaiyala
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rojas
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.|Department of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA.
authors.forename: Jarrad M
authors.initials: JM
authors.lastname: Scarlett
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Miles E
authors.initials: ME
authors.lastname: Matsen
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Jarrell T
authors.initials: JT
authors.lastname: Nelson
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Nikhil K
authors.initials: NK
authors.lastname: Acharya
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccinini
authors.affiliation: New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Darko
authors.initials: D
authors.lastname: Stefanovski
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Department of Veterans Affairs Medical Center, Seattle, WA.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Taborsky
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Department of Veterans Affairs Medical Center, Seattle, WA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.affiliation: University of Washington Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA mschwart@u.washington.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003080:Cold Temperature; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D010646:Phentolamine