title: Evidence that the brain of the conscious dog is insulin sensitive.
abstract: The aim of this study was to determine whether a selective increase in the level of insulin in the blood perfusing the brain is a determinant of the counterregulatory response to hypoglycemia. Experiments were carried out on 15 conscious 18-h-fasted dogs. Insulin was infused (2 mU/kg per min) in separate, randomized studies into a peripheral vein (n = 7) or both carotid and vertebral arteries (n = 8). This resulted in equivalent systemic insulinemia (84 +/- 6 vs. 86 +/- 6 microU/ml) but differing insulin levels in the head (84 +/- 6 vs. 195 +/- 5 microU/ml, respectively). Glucose was infused during peripheral insulin infusion to maintain the glucose level (56 +/- 2 mg/dl) at a value similar to that seen during head insulin infusion (58 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and similar hypoglycemia; steady state plasma epinephrine (792 +/- 198 vs. 2394 +/- 312 pg/ml), norepinephrine (404 +/- 33 vs. 778 +/- 93 pg/ml), cortisol (6.8 +/- 1.8 vs. 9.8 +/- 1.6 micrograms/dl) and pancreatic polypeptide (722 +/- 273 vs. 1061 +/- 255 pg/ml) levels were all increased to a greater extent during head insulin infusion (P < 0.05). Hepatic glucose production, measured with [3-3H]glucose, rose from 2.6 +/- 0.2 to 4.3 +/- 0.4 mg/kg per min (P < 0.01) in response to head insulin infusion but remained unchanged (2.6 +/- 0.5 mg/kg per min) during peripheral insulin infusion. Similarly, gluconeogenesis, lipolysis, and ketogenesis were increased twofold (P < 0.001) during head compared with peripheral insulin infusion. Cardiovascular parameters were also significantly higher (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog (a) the brain is directly responsive to physiologic elevations of insulin and (b) the response includes a profound stimulation of the autonomic nervous system with accompanying metabolic and cardiovascular changes.
authors.affiliation: Department of Medicine and Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: S N
authors.initials: SN
authors.lastname: Davis
authors.forename: C
authors.initials: C
authors.lastname: Colburn
authors.forename: R
authors.initials: R
authors.lastname: Dobbins
authors.forename: S
authors.initials: S
authors.lastname: Nadeau
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: D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D003243:Consciousness; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006885:Hydroxybutyrates / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000097:blood
chemical_list: D000090:Acetoacetates; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; C016635:acetoacetic acid; D005947:Glucose; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D009638:Norepinephrine; D004837:Epinephrine