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

Abstract

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.

Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides

“…In addition to a purely sensory role, the T1R-independent pathway may also have a role in regulating metabolism. Indeed, a robust cephalic phase insulin release (CPIR) can be induced by oral administration of glucose or sucrose, but not fructose in WT and Tas1r3 KO mice (36). The CPIR improved glucose tolerance in both strains, buttressing the physiological importance of this pathway.…”

Taste buds: cells, signals and synapses

“…Insulin release from the pancreas may also be stimulated by glucagon-like peptide 1 (GLP1; also known as incretin), which is secreted by sweet-sensing taste bud cells 30, 31 . Sugar-induced CPIR persists in Tas1r3 -knockout mice 32 and is mediated through the action of KATP channels 33 . Thus, at least two distinct and parallel sugar-sensing mechanisms seem to be initiated in taste buds: one that signals the perception of carbohydrate-rich foods (that is, sweet tastes, via T1R2–T1R3) and one that deploys a physiological reflex of insulin secretion (via a transporter).…”

Type 1 Taste Receptors in Taste and Metabolism

“…In humans and animals, saccharides elicit CPIR [45][46][47] . Although this might suggest that CPIR is mediated by T1Rs, the sensory mechanisms underlying CPIR are unclear.…”

“…HPS do not reliably elicit cephalic phase responses, which suggests that CPIR may be mediated by T1R-independent carbohydrate detection in the oral cavity [48][49][50] . More recently, it was shown that oral stimulation with glucose stimulates CPIR in T1R knockout animals [46] . And fructose, which does not bind SGLT1, fails to stimulate CPIR.…”