Insulin signaling in the central nervous system is critical for the normal sympathoadrenal response to hypoglycemia

Simon J. Fisher, Jens C. Brüning, Scott Lannon, C. Ronald Kahn

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Hypoglycemia, hypoglycemia unawareness, and impaired counterregulation are major challenges to the intensive management of type 1 diabetes. While the counterregulatory response to hypoglycemia is predominantly determined by the degree and duration of hypoglycemia, there is now evidence that insulin per se may influence the counterregulatory response to hypoglycemia. To define the role of insulin action in the central nervous system in regulating the counterregulatory response to hypoglycemia, mice with a brain/neuron-specific insulin receptor knockout (MERKO) and littermate controls were subjected to 90-min hyperinsulinemic (20 mU · kg-1 · min -1) -hypoglycemic (∼1.5 mmol/l) clamps. In response to hypoglycemia, epinephrine levels rose 5.7-fold in controls but only 3.5-fold in NIRKO mice. Similarly, in response to hypoglycemia, norepinephrine levels rose threefold in controls, but this response was almost completely absent in NIRKO mice. In contrast, glucagon and corticosterone responses to hypoglycemia were similar in both groups. Thus, insulin action in the brain is critical for full activation of the sympathoadrenal response to hypoglycemia, and altered neural insulin signaling could contribute to defective glucose counterregulation in diabetes.

Original languageEnglish
Pages (from-to)1447-1451
Number of pages5
Issue number5
StatePublished - May 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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