The involvement of the T1R3 receptor protein in the control of glucose metabolism in mice at different levels of glycemia

Муровец, В. О.; Bachmanov, Alexander A.; Travnikov, S. V.; Churikova, A. A.; Золотарев, В. А.

doi:10.1134/s0022093014040061

Cited by 14 publications

(18 citation statements)

References 51 publications

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“…3). In support of the observations by other studies, (i) disruption of the GLP-1 receptor action in mice caused IFG and IGT [40]; (ii) reduced glucose tolerance was observed in the TAS1R3 −/− mice [41]. Additionally, we also observed the elevated plasma glucagon levels in 3DG-treated in addition to decreased plasma insulin levels (Fig.…”

Section: Discussionsupporting

confidence: 92%

Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats

Zhang

Song

Zhou

et al. 2016

Diabetol Metab Syndr

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BackgroundOur recent findings support the idea that 3-deoxyglucosone (3DG), a dietary composition, has been suggested as an independent factor for the development of prediabetes. Secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. Since low oral bioavailability of 3DG has been indicated in a single administration study, in the present study we examined if 3DG is capable of accumulating in intestinal tissue of rats after 2-week administration of 3DG, and the 3DG treatment affects GLP-1 secretion and glucose tolerance.MethodsRats were administered by gastric gavage for 2 weeks. We measured 3DG contents of intestinal tissues (by HPLC), plasma levels of total GLP-1 (by ELISA), insulin and glucagon (both by radioimmunoassay) and blood glucose concentrations. The expressions of the sweet receptor subunits (TAS1R2, TAS1R3) and its downstream molecule TRPM5 in duodenum and colon tissues of rats were quantified by WB. We examined GLP-1 secretion in enteroendocrine STC-1 cells exposured to 3DG.Results3DG treatment for 2 weeks increased 3DG content of intestinal tissues, fasting blood glucose concentration, and reduced plasma concentrations of GLP-1 and insulin at fasting and 15 and 180 min after the glucose load and oral glucose tolerance in conjunction with increased plasma glucagon concentrations. The expressions of TAS1R2, TAS1R3 and TRPM5 were shown to be reduced whereas 3DG treatment did not affect plasma dipeptidyl peptidase-4 activity, indicating an impaired GLP-1 secretion in 3DG-treated rats. This idea was further supported by the fact that exposure to 3DG directly decrease GLP-1 secretion in STC-1.ConclusionIt is the first demonstration that 3DG was capable of accumulating in intestinal tissue and thereby decreased secretion of GLP-1 and insulin in a similar manner. 3DG-treated rats developed impaired glucose regulation (IGR) with obviously pancreatic islet cell dysfunction. It is further concluded that a decrease in the biological function of GLP-1 resulting from the decreased GLP-1 secretion is the most likely mechanism for the impaired insulin secretion, which ultimately promoted the development of IGR. These results will also contribute to a better understanding of the significance for restoring physiological GLP-1 secretion.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-016-0194-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats

Zhang

Song

Zhou

et al. 2016

Diabetol Metab Syndr

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“…The mice were kept in a separate room as the following conditions: 22±2°C, 50±10% relative humidity, 12/12 h light-dark cycle [26], with free access to water. The 60 mice were acclimatized for 1 week, and randomly divided into two groups: 1) standard feed group, n = 10 mice, and 2) high sugar/high fat group [27–28], n = 50 mice. The ingredients for the high sugar & high fat mice feed are shown in S1 Table.…”

Section: Methodsmentioning

confidence: 99%

“…At the end of four weeks’ gavage, all mice were fasted for 12 h (from 20:00PM to 8:00AM at next day), and 2 g/kg (body weight) glucose solution [28] was administered orally using gavage [31]. Samples of blood glucose were collected from the tail vein at 30, 60 and 120 min after gavage.…”

Section: Methodsmentioning

confidence: 99%

Leaf Extract from Lithocarpus polystachyus Rehd. Promote Glycogen Synthesis in T2DM Mice

Wang

Huang

et al. 2016

PLoS ONE

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The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice. The biochemical parameters were measured including blood glucose and blood lipid level, liver biochemical indexes, and hepatic glycogen. The relative expression of glycometabolism-related genes was detected. The effect of leaf extracts on physiological glucose flux in liver tissue from control and T2DM mice was also investigated. Body weight of experimental T2DM mice increased significantly after the first week, but stabilized over the subsequent three weeks; body weight of all other groups did not change during the four weeks’ study. After four weeks, all treatment groups decreased blood glucose, and treatment with leaf extract had numerous positive effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK), glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with trilobatin or phloridzin accelerated liver glycogen synthesis, decreased oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin. Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after treatment with phloridzin. Our data indicate that leaf extract from L. polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and oxidative stress in T2DM mice. From this study, we draw conclusions that L. polystachyus promoted glycogen synthesis in T2DM mice, and that the active compounds were not only the trilobatin or phloridzin.

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“…In TAS1R3 knockout mice, Murovets et al . [14*] reported that glucose tolerance was reduced, accompanied by increased insulin resistance, indicating that this component of the sweet receptor is involved in gut sugar-sensing pathways, probably involving impaired release of GLP-1. The broad distribution of TAS1R3, with high abundance particularly in the central nervous system and pancreas, however supports extraintestinal pathways as well.…”

Section: Taste Receptor-related Release Of Glpsmentioning

confidence: 99%

“…One practical method to physiologically release endogenous GLP-2 is through the ingestion of ligands for receptors expressed on the L cell apical membrane that release GLP-2 when activated. In this regard, artificial sweeteners, which are simply high-affinity ligands for the sweet taste receptor (TASR1R2/3), release GLP-1 and GLP-2 [8,14**], with beneficial effects on glycemic control and on the intestinal mucosa. Since artificial sweeteners are in common clinical use and are recognized as food additives by the FDA, their non-FDA approved use in diabetes, FBD, and IBD deserves further study although some epidemiologic studies suggest that these substances may be ineffective or even detrimental [43].…”

Section: Artificial Sweetenersmentioning

confidence: 99%

Gastroduodenal mucosal defense mechanisms

Said

Kaji

Kaunitz

2015

Current Opinion in Gastroenterology

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Purpose of Review To highlight recent developments in the field of gastroduodenal mucosal defense with emphasis on lumen-gut interactions. Recent Findings There has been a growing interest in the physiological functions of luminal chemosensors present from tongue to colon that detect organic molecules in the luminal content associated with nutrient ingestion, usually associated with specialized cells, in particular the enteroendocrine cells. These receptors transduce the release of peptide hormones, in particular proglucagon-derived products such as the glucagon-like-peptides (GLPs), which have profound effects on gut function and on metabolism. Luminal chemosensors transduce GLP release in response to changes in the cellular environment, as part of the mechanism of nutrient chemosensing. GLP-2 has important trophic effects on the intestinal mucosa, including increasing the proliferation rate of stem cells and reducing transmucosal permeability to ions and small molecules, in addition to increasing the rate of duodenal bicarbonate secretion. GLP-1, although traditionally considered an incretin that enhances the effect of insulin on peripheral tissues, also has trophic effects on the intestinal epithelium. Summary A better understanding of the mechanisms that mediate GLP release can further illuminate the importance of nutrient chemosensing as an important component of the mechanism that mediates the trophic effects of luminal nutrients. GLP-1 and -2 are already in clinical use for the treatment of diabetes and intestinal failure. Improved understanding of the control of their release and their end-organ effects will identify new clinical indications and interventions that enhance their release.

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The involvement of the T1R3 receptor protein in the control of glucose metabolism in mice at different levels of glycemia

Cited by 14 publications

References 51 publications

Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats

Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats

Leaf Extract from Lithocarpus polystachyus Rehd. Promote Glycogen Synthesis in T2DM Mice

Gastroduodenal mucosal defense mechanisms

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