Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones - PubMed (original) (raw)

Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones

Zaza Kokrashvili et al. Am J Clin Nutr. 2009 Sep.

Abstract

Many of the receptors and downstream signaling elements involved in taste detection and transduction are also expressed in enteroendocrine cells where they underlie the chemosensory functions of the gut. In one well-known example of gastrointestinal chemosensation (the "incretin effect"), it is known that glucose that is given orally, but not systemically, induces secretion of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide (the incretin hormones), which in turn regulate appetite, insulin secretion, and gut motility. Duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Knockout mice that lack gustducin or the sweet taste receptor subunit T1r3 have deficiencies in secretion of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide and in the regulation of plasma concentrations of insulin and glucose in response to orally ingested carbohydrate-ie, their incretin effect is dysfunctional. Isolated small intestine and intestinal villi from gustducin null mice displayed markedly defective glucagon-like peptide 1 secretion in response to glucose, indicating that this is a local circuit of sugar detection by intestinal cells followed by hormone secretion from these same cells. Modulating hormone secretion from gut "taste cells" may provide novel treatments for obesity, diabetes, and malabsorption syndromes.

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Figures

FIGURE 1

FIGURE 1

A: Indirect immunofluorescence staining of mouse duodenum showing co-expression of _α_-gustducin (_α_-gust) with glucagon-like peptide 1 (GLP-1), and GLP-2. Intrinsic fluorescence of green fluorescent protein (GFP) shows the expression of GFP and GLP-2 in the _α_-gustducin-expressing cells of _α_-gustducin–GFP transgenic mice. B: Indirect immunofluorescence of mouse jejunum showing the co-expression of _α_-gustin with GLP-1, GLP-2, and peptide YY (PYY). Bars, 15 _μ_m. Data are modified with permission from reference .

FIGURE 2

FIGURE 2

Secretion of glucagon-like peptide 1 (GLP-1) (A) and insulin (B) in response to glucose gavage (5 g/kg body weight) in _α_-gustducin knockout (α-gust−/−) mice and wild-type (α-gust+/+) mice. (C) Postfasting plasma glucose concentrations after feeding standard rodent diet in α-gust−/− mice and α-gust+/+ mice. (D) Secretion of GLP-1 in response to 10% glucose injected into surgically isolated duodenum in α-gust−/− mice, T1r3 knockout (T1r3−/−) mice, and α-gust+/+ mice. The duodenum was ligated away from the stomach and the rest of the intestines, and circulatory contact was maintained. (E) Secretion of GLP-1 ex vivo from minced proximal duodenum from α-gust−/− and α-gust+/+ mice in response to the addition of 10% glucose to the culture medium. (F) Secretion of GLP-1 ex vivo from isolated duodenal villi from α-gust−/− and α-gust+/+ mice in response to the addition of 10% glucose to the culture medium. For in vivo experiments, n = 5–12 animals/genotype; in vitro experiments were carried out in triplicate and replicated at least twice. All values are means ± SEMs. *,**,*** Statistical significance was determined by ANOVA: *P < 0.05, **P < 0.01, ***P < 0.001. Data are modified with permission from Reference .

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