Vasoactive Intestinal Peptide–Null Mice Demonstrate Enhanced Sweet Taste Preference, Dysglycemia, and Reduced Taste Bud Leptin Receptor Expression

  1. Josephine M. Egan1
  1. 1National Institutes of Health, National Institute on Aging, Baltimore, Maryland;
  2. 2Department of Psychiatry and Behavioral Sciences, Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
  1. Corresponding author: Josephine Egan, eganj{at}
  1. B.M. and Y.-K.S. contributed equally to this study.


OBJECTIVE It is becoming apparent that there is a strong link between taste perception and energy homeostasis. Recent evidence implicates gut-related hormones in taste perception, including glucagon-like peptide 1 and vasoactive intestinal peptide (VIP). We used VIP knockout mice to investigate VIP's specific role in taste perception and connection to energy regulation.

RESEARCH DESIGN AND METHODS Body weight, food intake, and plasma levels of multiple energy-regulating hormones were measured and pancreatic morphology was determined. In addition, the immunocytochemical profile of taste cells and gustatory behavior were examined in wild-type and VIP knockout mice.

RESULTS VIP knockout mice demonstrate elevated plasma glucose, insulin, and leptin levels, with no islet β-cell number/topography alteration. VIP and its receptors (VPAC1, VPAC2) were identified in type II taste cells of the taste bud, and VIP knockout mice exhibit enhanced taste preference to sweet tastants. VIP knockout mouse taste cells show a significant decrease in leptin receptor expression and elevated expression of glucagon-like peptide 1, which may explain sweet taste preference of VIP knockout mice.

CONCLUSIONS This study suggests that the tongue can play a direct role in modulating energy intake to correct peripheral glycemic imbalances. In this way, we could view the tongue as a sensory mechanism that is bidirectionally regulated and thus forms a bridge between available foodstuffs and the intricate hormonal balance in the animal itself.


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    • Received June 10, 2009.
    • Accepted January 28, 2010.

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  1. Diabetes vol. 59 no. 5 1143-1152
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