Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells

Kojima, Itaru; Nakagawa, Yuko; Hamano, Kunihisa; Medina, Johan; Li, Longfei; Nagasawa, Mitsuru

doi:10.1248/bpb.b14-00895

Cited by 27 publications

(31 citation statements)

References 34 publications

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“…T1r3 likely plays a subsidiary role in the receptor function of T1r, such as inter-subunit conformational coupling and G-protein coupling24, or membrane trafficking of T1r heterodimers40. In addition, the ligand binding properties of T1r3 observed in this study may substantiate previous observations that T1r3 alone responds to chemicals in certain situations294142, which may exist in tongue and palate epithelium, as well as in various tissues throughout the body, expressing T1r3 and not T1r1 or T1r2 (refs 3, 43). …”

Section: Discussionsupporting

confidence: 87%

Structural basis for perception of diverse chemical substances by T1r taste receptors

et al. 2017

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The taste receptor type 1 (T1r) family perceives ‘palatable' tastes. These receptors function as T1r2-T1r3 and T1r1-T1r3 heterodimers to recognize a wide array of sweet and umami (savory) tastes in sugars and amino acids. Nonetheless, it is unclear how diverse tastes are recognized by so few receptors. Here we present crystal structures of the extracellular ligand-binding domains (LBDs), the taste recognition regions of the fish T1r2-T1r3 heterodimer, bound to different amino acids. The ligand-binding pocket in T1r2LBD is rich in aromatic residues, spacious and accommodates hydrated percepts. Biophysical studies show that this binding site is characterized by a broad yet discriminating chemical recognition, contributing for the particular trait of taste perception. In contrast, the analogous pocket in T1r3LBD is occupied by a rather loosely bound amino acid, suggesting that the T1r3 has an auxiliary role. Overall, we provide a structural basis for understanding the chemical perception of taste receptors.

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Section: Discussionsupporting

confidence: 87%

Structural basis for perception of diverse chemical substances by T1r taste receptors

et al. 2017

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“…The absence of T1R2 gene expression, but detection of T1R3 in mouse EC cells, indicates that the T1R2/T1R3 receptor is unlikely to be a significant path to 5‐HT release . Rather, a T1R3 homodimer may exist, which has been previously shown to act as a glucose‐sensing receptor in pancreatic β‐cells . Alternately, transcript expression can be seen without the presence of a functional protein product .…”

Section: Discussionmentioning

confidence: 97%

“…43 Rather, a T1R3 homodimer may exist, which has been previously shown to act as a glucose-sensing receptor in pancreatic β-cells. 44,45 Alternately, transcript expression can be seen without the presence of a functional protein product. 45 Thus, the expression of T1R3 is not necessarily indicative of a functional sweet taste receptor.…”

Section: Discussionmentioning

confidence: 99%

The nutrient‐sensing repertoires of mouse enterochromaffin cells differ between duodenum and colon

Martin

Lumsden

Young

et al. 2017

Neurogastroenterology Motil

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“…This effect could also depend on the diet content, for instance, sucralose consumption (≥5 days) in combination with an imbalanced diet has been shown to trigger a neuronal response which stimulates food intake in a fruit fly model [29]; nevertheless, in the present study no significant differences were found in the intake of macronutrients in any of the groups before and after the intervention for 10 weeks. In view of these results, it seems that sucralose has metabolic effects that interfere with glucose and insulin homeostasis, possibly due to different mechanisms such as gut microbiota dysbiosis or sweet taste receptors expressed in the digestive system [30][31][32], which play an important role in both glucose absorption and insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial

Bueno‐Hernández

Esquivel-Velázquez

Alcántara-Suárez

et al. 2020

Nutr J

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Background: Non-nutritive sweeteners (NNS) are widely consumed by humans due to their apparent innocuity, especially sucralose. However, several studies link sucralose consumption to weight gain and metabolic derangements, although data are still contradictory. Objective: To determine the effect of acute and chronic consumption of sucralose on insulin and glucose profiles in young healthy adults. Material and methods: This was a randomized, parallel, double-blind, placebo-controlled trial conducted in healthy young adults from 18 to 35 years old, without insulin resistance. A hundred thirty seven participants were randomized into three groups: a) volunteers receiving 48 mg sucralose, b) volunteers receiving 96 mg sucralose, and c) controls receiving water as placebo. All participants underwent a 3-h oral glucose tolerance test (OGTT) preceded by consuming sucralose or placebo 15 min before glucose load, at two time points: week zero (Wk0) and week ten (Wk10). Serum insulin and glucose were measured every 15 min during both OGTTs.

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Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells

Cited by 27 publications

References 34 publications

Structural basis for perception of diverse chemical substances by T1r taste receptors

Structural basis for perception of diverse chemical substances by T1r taste receptors

The nutrient‐sensing repertoires of mouse enterochromaffin cells differ between duodenum and colon

Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial

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