title: Brain of the conscious dog is sensitive to physiological changes in circulating insulin.
abstract: The aim of this study was to determine whether a selective, physiologically relevant increase in blood-borne insulin perfusing the brain has an impact on the counterregulatory response to hypoglycemia. Experiments were carried out on 12 conscious 18-h-fasted dogs. Insulin was infused (1 mU x kg(-1) x min(-1)) in separate, randomized studies into a peripheral vein (n = 6) or both carotid and vertebral arteries (n = 6). This resulted in equivalent systemic insulinemia (38 +/- 2 vs. 35 +/- 5 microU/ml) but differing head insulin levels (38 +/- 2 microU/ml during peripheral infusion and an estimated 90 microU/ml during head insulin infusion). Glucose was infused during peripheral insulin infusion to equate the level of hypoglycemia (58 +/- 2 mg/dl) to that obtained during head insulin infusion (57 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and hypoglycemia, incremental area under the curve responses for epinephrine, glucagon and cortisol were increased during head insulin infusion (P < 0.05). Net hepatic glucose output, gluconeogenesis, and lipolysis were increased 50-100% (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog 1) physiologically relevant increases of blood-borne insulin to the head can amplify neuroendocrine and metabolic counterregulatory responses and 2) glucagon secretion can be regulated, in part, by neural efferent activity.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Davis
authors.forename: B
authors.initials: B
authors.lastname: Dunham
authors.forename: K
authors.initials: K
authors.lastname: Walmsley
authors.forename: C
authors.initials: C
authors.lastname: Shavers
authors.forename: D
authors.initials: D
authors.lastname: Neal
authors.forename: P
authors.initials: P
authors.lastname: Williams
authors.forename: A D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000502:physiology*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis; D005990:Glycerol / Q000378:metabolism; D006728:Hormones / Q000097:blood; D007328:Insulin / Q000097:blood*; D007657:Ketone Bodies / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D007657:Ketone Bodies; D019344:Lactic Acid; D000409:Alanine; D005990:Glycerol