Brain of the conscious dog is sensitive to physiological changes in circulating insulin

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.kg(-1).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 mu U/ml) but differing head insulin levels (38 +/- 2 mu U/ml during peripheral infusion and an estimated 90 mu U/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.