Insulin Signals Through the Dorsal Vagal Complex to Regulate Energy Balance

  1. Tony K.T. Lam1,2,3,4
  1. 1Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  2. 2Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  3. 3Department of Physiology, University of Toronto, Toronto, Ontario, Canada
  4. 4Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
  1. Corresponding author: Tony K.T. Lam, tony.lam{at}uhnres.utoronto.ca.

Abstract

Insulin signaling in the hypothalamus regulates food intake and hepatic glucose production in rodents. Although it is known that insulin also activates insulin receptor in the dorsal vagal complex (DVC) to lower glucose production through an extracellular signal–related kinase 1/2 (Erk1/2)–dependent and phosphatidylinositol 3-kinase (PI3K)–independent pathway, it is unknown whether DVC insulin action regulates food intake. We report here that a single acute infusion of insulin into the DVC decreased food intake in healthy male rats. Chemical and molecular inhibition of Erk1/2 signaling in the DVC negated the acute anorectic effect of insulin in healthy rats, while DVC insulin acute infusion failed to lower food intake in high fat–fed rats. Finally, molecular disruption of Erk1/2 signaling in the DVC of healthy rats per se increased food intake and induced obesity over a period of 2 weeks, whereas a daily repeated acute DVC insulin infusion for 12 days conversely decreased food intake and body weight in healthy rats. In summary, insulin activates Erk1/2 signaling in the DVC to regulate energy balance.

Footnotes

  • Received July 3, 2013.
  • Accepted November 19, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

Articles citing this article

| Table of Contents

This Article

  1. Diabetes vol. 63 no. 3 892-899
  1. Supplementary Data
  2. All Versions of this Article:
    1. db13-1044v1
    2. 63/3/892 most recent