Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice

Am J Physiol Regul Integr Comp Physiol. 2015 Sep;309(5):R552-60. doi: 10.1152/ajpregu.00056.2015. Epub 2015 Jul 8.


Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.

Keywords: T1r3; cephalic-phase insulin release; glucose tolerance; mice; sweet taste.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Behavior, Animal / drug effects
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Carbohydrates / administration & dosage*
  • Carbohydrates / blood
  • Chorda Tympani Nerve / drug effects
  • Chorda Tympani Nerve / metabolism
  • Food Preferences / drug effects
  • Fructose / administration & dosage
  • Genotype
  • Glucose / administration & dosage
  • Glucose Tolerance Test
  • Injections
  • Insulin / blood*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects*
  • Sucrose / administration & dosage
  • Sweetening Agents / administration & dosage*
  • Taste / drug effects*
  • Time Factors


  • Blood Glucose
  • Carbohydrates
  • Insulin
  • Receptors, G-Protein-Coupled
  • Sweetening Agents
  • taste receptors, type 1
  • Fructose
  • Sucrose
  • Glucose