Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells

Reimann, Frank; Gribble, Fiona M.

doi:10.2337/diabetes.51.9.2757

Cited by 255 publications

(262 citation statements)

References 57 publications

(47 reference statements)

Supporting

Mentioning

237

Contrasting

Order By: Relevance

“…The finding that G␣ gust and T1Rs are expressed in enteroendocrine cells, whereas SGLT1 is expressed in enterocytes, implies that a chemical signaling event takes place between the chemosensory enteroendocrine cells and absorptive enterocytes. Enteroendocrine cells, in response to luminal nutrients, secrete endocrine hormones including cholecystokinin (CCK), peptide tyrosine tyrosine (PYY), neurotensin, GLP-1, GLP-2, and GIP (18,19,(22)(23)(24). GLP-1 and GIP, known as incretins, are secreted in response to dietary sugars, and influence glucose transport, metabolism, and homeostasis (25).…”

Section: Discussionmentioning

confidence: 99%

“…Because of practical difficulties in harvesting adequate numbers of viable enteroendocrine cells of specific subtypes, we turned to intestinal endocrine cell lines. GLUTag and STC-1 cells, two mouse enteroendocrine cell lines, have been shown to secrete hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP), in response to glucose (17,18). GLUTag cells also respond to fructose and nonmetabolizable glucose analogs (18,19).…”

Section: Sucralose Activates Sweet Taste Receptors On Enteroendocrinementioning

confidence: 99%

“…GLUTag and STC-1 cells, two mouse enteroendocrine cell lines, have been shown to secrete hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP), in response to glucose (17,18). GLUTag cells also respond to fructose and nonmetabolizable glucose analogs (18,19). STC-1 cells have been shown to express T1Rs, T2Rs, and taste G proteins (11,12).…”

Section: Sucralose Activates Sweet Taste Receptors On Enteroendocrinementioning

confidence: 99%

See 2 more Smart Citations

T1R3 and gustducin in gut sense sugars to regulate expression of Na ⁺ -glucose cotransporter 1

Margolskee

Dyer

Kokrashvili

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

774

843

View full text Add to dashboard Cite

Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or ␣-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 upregulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.carbohydrate absorption ͉ gastrointestinal chemosensation ͉ glucose sensor ͉ glucose uptake T o date, the only identified sugar sensors in the mammalian gastrointestinal tract are those involved in taste transduction (1). Although the gut epithelium senses luminal sugars and modulates its glucose absorptive capacity accordingly, the nature of the sugar-sensing molecule(s) and downstream events remain unknown. Several studies have shown that in many species expression of the intestinal sodium-dependent glucose transporter 1 (SGLT1) is directly regulated by monosaccharides in the lumen of the gut independently of metabolism and appears to involve a G protein-linked second messenger pathway (2-6). Furthermore, the addition of membrane-impermeable glucose analogues to the lumen of the intestine stimulates SGLT1 expression, implying that a glucose sensor on luminal membranes is involved (6).In taste cells, the detection of sugars and sweeteners depends on T1R2ϩT1R3, a heterodimer of type 1 taste receptor subunits (T1Rs) (7,8). The taste receptor cells of the anterior tongue that express T1R2ϩT1R3 typically also express gustducin, a transducin-like heterotrimeric G protein (9). Gustducin's ␣-subunit (G␣ gust ) has been detected in brush cells of the rat stomach, duodenum, and pancreatic ducts (10). G␣ gust and bitter-responsive type 2 taste receptors (T2Rs) are expressed in mouse intestinal endocrine cells and in the murine enteroendocrine cell line STC-1 (11).We reported previously that T1R taste receptors and G␣ gust are expressed in the mouse small intestinal epithelium and proposed that they function as luminal sugar sensors to control SGLT1 expression in response to dietary sugar (12). Here, we provide three lines of evidence in favor of T1R taste receptors an...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Sucralose Activates Sweet Taste Receptors On Enteroendocrinementioning

confidence: 99%

Section: Sucralose Activates Sweet Taste Receptors On Enteroendocrinementioning

confidence: 99%

See 1 more Smart Citation

T1R3 and gustducin in gut sense sugars to regulate expression of Na ⁺ -glucose cotransporter 1

Margolskee

Dyer

Kokrashvili

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

774

843

View full text Add to dashboard Cite

show abstract

“…The T1R2ϩ3 heterodimer should, by analogy to the tongue, respond to various sweet-tasting molecules as diverse as sucrose, saccharin, acesulfame K, and sucralose (32,47). Furthermore, it has been demonstrated in two mouse enteroendocrine cell lines, GLUTag and STC-1, that sweet taste receptors are colocalized with GLP-1 and GIP (22,37) and that sucralose stimulates secretion of GLP-1 and GIP from GLUTag cells (28). Mice that lack ␣-gustducin show markedly defective GLP-1 secretion in response to glucose (21).…”

Section: Discussionmentioning

confidence: 99%

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

Bellon

Wishart

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

216

160

View full text Add to dashboard Cite

show abstract

“…It is known that oral glucose can stimulate secretion of the insulin secretagogue hormone glucagonlike peptide-1 (GLP-1) from the intestinal L cells, while intravenous glucose is ineffective. Glucose and sulfonylureas have also been reported to trigger the generation of action potentials in a GLP-1-secreting cell line, suggesting a role for K ATP channels in this function [9]. It might, therefore, be of interest to evaluate GLP-1 secretion before and after glibenclamide treatment in patients with KCNJ11 mutation.…”

mentioning

confidence: 99%

Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation

et al. 2005

View full text Add to dashboard Cite

Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells

Cited by 255 publications

References 57 publications

T1R3 and gustducin in gut sense sugars to regulate expression of Na ⁺ -glucose cotransporter 1

T1R3 and gustducin in gut sense sugars to regulate expression of Na ⁺ -glucose cotransporter 1

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation

Contact Info

Product

Resources

About

Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells

Cited by 255 publications

References 57 publications

T1R3 and gustducin in gut sense sugars to regulate expression of Na + -glucose cotransporter 1

T1R3 and gustducin in gut sense sugars to regulate expression of Na + -glucose cotransporter 1

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation

Contact Info

Product

Resources

About

T1R3 and gustducin in gut sense sugars to regulate expression of Na ⁺ -glucose cotransporter 1

T1R3 and gustducin in gut sense sugars to regulate expression of Na ⁺ -glucose cotransporter 1