Glucose elicits cephalic-phase insulin release in mice by activating K_ATPchannels in taste cells

Abstract

The taste of sugar elicits cephalic-phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647, or a nonmetabolizable sugar analog. The only taste stimuli that elicited CPIR were glucose and the glucose-containing saccharides (sucrose, maltose, Polycose). When we mixed an α-glucosidase inhibitor (acarbose) with the latter three saccharides, the mice no longer exhibited CPIR. This revealed that the carbohydrates were hydrolyzed in the mouth, and that the liberated glucose triggered CPIR. We also found that increasing the intensity or duration of oral glucose stimulation caused a corresponding increase in CPIR magnitude. To identify the components of the glucose-specific taste-signaling pathway, we examined the necessity of Calhm1, P2X2+P2X3, SGLT1, and Sur1. Among these proteins, only Sur1 was necessary for CPIR. Sur1 was not necessary, however, for taste-mediated attraction to sugars. Given that Sur1 is a subunit of the ATP-sensitive K channel (K) channel and that this channel functions as a part of a glucose-sensing pathway in pancreatic β-cells, we asked whether the K channel serves an analogous role in taste cells. We discovered that oral stimulation with drugs known to increase (glyburide) or decrease (diazoxide) K signaling produced corresponding changes in glucose-stimulated CPIR. We propose that the K channel is part of a novel signaling pathway in taste cells that mediates glucose-induced CPIR.

Flavor preferences conditioned by nutritive and non-nutritive sweeteners in mice

“…Furthermore, one or more of these sensors are implicated in the cephalic-phase insulin response (CPIR) to sugars because T1r3 KO and B6 wildtype mice display comparable CPIRs to oral glucose and sucrose [17]. However, fructose, saccharin and sucralose do not elicit a CPIR in B6 mice indicating that the sugar-sensing CPIR pathway cannot account for the differential preference conditioning effects of these three sweeteners [16,17]. …”

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).…”

Sensing Senses: Optical Biosensors to Study Gustation

“…Along these lines, G-proteins other than gustducin are likely also involved in the signaling cascade [275,331] as well as other second messengers than Ca 2+ , such as cAMP [141,165]. Moreover, sweet signal transduction mechanisms may exist that bypass the activation of sweet taste receptors and instead use glucose transporters (GLUT) [86,87,332]. The pathway usage might be different even for compounds falling into the same taste modality [139], as it might be true for nutritive sugars and synthetic sweeteners or bitter compounds utilizing a PLCβ2-independent pathway at higher concentrations [333].…”