The downregulation of sweet taste receptor signaling in enteroendocrine L-cells mediates 3-deoxyglucosone-induced attenuation of high glucose-stimulated GLP-1 secretion

Wang, Fei; Song, Xiudao; Zhou, Liang; Liang, Guoqiang; Huang, Fei; Jiang, Guilin; Zhang, Lurong

doi:10.1080/13813455.2017.1419366

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…If so, competitive inhibition between 3DG and high glucose may emerge. Interestingly, we previously reported that acute exposure to 3DG reduces GLP-1 secretion by downregulating the STR expression under high-glucose conditions [21]. The above results could be explained by the idea that 3DG treatment may partially occupy STR substrate binding sites under high-glucose conditions and high concentrations of glucose may be more potent and more effective than 3DG.…”

Section: Discussionmentioning

confidence: 92%

“…Previously, we have reported that an acute administration of 3DG leads to a decrease in glucose-stimulated GLP-1 secretion in vivo [17] and in vitro [21]. In this study, we examined the effect of an acute administration of 3DG on basal GLP-1 secretion in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, our previous study found that acute 3DG administration by gastric gavage resulted in the impairment in oral glucose-stimulated GLP-1 secretion in rats [17]. Furthermore, acute exposure of STC-1 cells to 3DG in the presence of high glucose (25 mM) for one hour is able to downregulate the protein expression level of STR, thus decreasing STR-mediated GLP-1 secretion [21]. It is unknown, however, whether acute exposure to 3DG may impair GLP-1 secretion under basal conditions.…”

Section: Introductionmentioning

confidence: 99%

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3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions

Song

Wang

et al. 2019

International Journal of Endocrinology

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3-Deoxyglucosone (3DG) is derived from D-glucose during food processing and storage and under physiological conditions. We reported that glucagon-like peptide-1 (GLP-1) secretion in response to an oral glucose load in vivo and high-glucose stimulation in vitro was decreased by acute 3DG administration. In this study, we determined the acute effect of 3DG on GLP-1 secretion under basal conditions and investigated the possible mechanisms. Normal fasting rats were given a single acute intragastric administration of 50 mg/kg 3DG. Plasma basal GLP-1 levels and duodenum 3DG content and sweet taste receptor expression were measured. STC-1 cells were acutely exposed to 3DG (80, 300, and 1000 ng/ml) for 1 h under basal conditions (5.6 mM glucose), and GLP-1 secretion, intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and molecular expression of STR signaling pathway were measured. Under the fasted state, plasma GLP-1 levels, duodenum 3DG content, and duodenum STR expression were elevated in 3DG-treated rats. GLP-1 secretion was increased in 3DG-treated cells under either 5.6 mM glucose or glucose-free conditions. 3DG-induced acute GLP-1 secretion from STC-1 cells under 5.6 mM glucose was inhibited in the presence of the STR inhibitor lactisole, which was consistent with the observation under glucose-free conditions. Moreover, acute exposure to 3DG increased the protein expression of TAS1R2 and TAS1R3 under either 5.6 mM glucose or glucose-free conditions, with affecting other components of STR signaling pathway, including the upregulation of transient receptor potential channel type M5 TRPM5 and the increment of intracellular Ca2+ concentration. In summary, the glucose-free condition was used to first demonstrate the involvement of STR in 3DG-induced acute GLP-1 secretion. These results first showed that acute 3DG administration induces basal GLP-1 secretion in part through upregulation of STR expression.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions

Song

Wang

et al. 2019

International Journal of Endocrinology

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“…Several parameters have been proposed to affect the secretion and concentration of GLP-1 including glucose [19], fat [19], bile acids [20], inflammatory markers [21, 22], 3-deoxyglucosone [23] (generated from carbohydrates) and the presence of obesity [24] and type 2 diabetes [18].…”

Section: Discussionmentioning

confidence: 99%

Greater glucagon-like peptide-1 responses to oral glucose are associated with lower central and peripheral blood pressures

Lundgren

Færch

Witte

et al. 2019

Cardiovasc Diabetol

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Background and aim: Cardiovascular diseases (CVDs) are globally the leading cause of death and hypertension is a significant risk factor. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with decreases in blood pressure and CVD risk. Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD. Methods: This cross-sectional study included 837 Danish individuals from the ADDITION-PRO cohort (52% men, median (interquartile range) age 65.5 (59.8 to 70.7) years, BMI 26.1 (23.4 to 28.5) kg/m 2 , without antihypertensive treatment and known diabetes). All participants received an oral glucose tolerance test with measurements of GLP-1 at 0, 30 and 120 min. Aortic stiffness was assessed by pulse wave velocity (PWV). The associations between GLP-1 response and central and brachial blood pressure (BP) and PWV were assessed in linear regression models adjusting for age and sex. Results: A greater GLP-1 response was associated with lower central systolic and diastolic BP of − 1.17 mmHg (95% confidence interval (CI) − 2.07 to − 0.27 mmHg, P = 0.011) and − 0.74 mmHg (95% CI − 1.29 to − 0.18 mmHg, P = 0.009), respectively, as well as lower brachial systolic and diastolic BP of − 1.27 mmHg (95% CI − 2.20 to − 0.33 mmHg, P = 0.008) and − 1.00 (95% CI − 1.56 to − 0.44 mmHg, P = 0.001), respectively. PWV was not associated with GLP-1 release (P = 0.3). Individuals with the greatest quartile of GLP-1 response had clinically relevant lower BP measures compared to individuals with the lowest quartile of GLP-1 response (central systolic BP: − 4.94 (95% CI − 8.56 to − 1.31) mmHg, central diastolic BP: − 3.05 (95% CI − 5.29 to − 0.80) mmHg, brachial systolic BP: − 5.18 (95% CI − 8.94 to − 1.42) mmHg, and brachial diastolic BP: − 2.96 (95% CI − 5.26 to − 0.67) mmHg). Conclusion: Greater glucose-stimulated GLP-1 responses were associated with clinically relevant lower central and peripheral blood pressures, consistent with beneficial effects on the cardiovascular system and reduced risk of CVD and mortality.

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“…A smaller study in twins showed that in monozygotic pairs discordant for BMI and liver fat the GLP-1 secretion was reduced at 60 min during an OGTT [45]. Furthermore, an experimental study by Wang et al has shown interesting results where 3-deoxyglucosone (3DG), a precursor for advanced glycation end-products known to be able to induce glucose intolerance, reduces GLP-1 release [46]. Against this background of GLP-1 level alterations our study finding with elevated GLP-1 levels in subjects with a recent ischemic stroke add information.…”

Section: Strengths and Weaknesses In Relation To Other Studiesmentioning

confidence: 99%

GLP-1 secretion in acute ischemic stroke: association with functional outcome and comparison with healthy individuals

Larsson

Patrone

Euler

et al. 2019

Cardiovasc Diabetol

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Background Glucagon-like peptide-1 (GLP-1) treatment has been shown to reduce stroke incidence in diabetes and also to be neuroprotective in experimental stroke models. The prognostic value of endogenous levels of GLP-1 in the recovery phase after stroke remains to be elucidated. The aim of the study was to investigate the potential association between GLP-1 levels and functional outcome after stroke and to determine whether GLP-1 is altered in the acute phase of stroke compared to 3 months post stroke and to healthy controls. Methods Fasting GLP-1 was measured on hospital day 2–4 in patients without previously known diabetes (n = 59) that received recombinant tissue plasminogen activator (rtPA) for ischemic stroke. Fasting GLP-1 was measured again after 3 months and neurologic outcome was measured as modified Rankin Scale (mRS). mRS ≥ 2 was considered as unfavorable outcome. A control group of healthy individuals (n = 27) was recruited and their fasting GLP-1 was measured. Results Fasting GLP-1 was higher in the patients that suffered a stroke compared to healthy controls (25.1 vs. 18.0 pmol/L; p = 0.004). The GLP-1 levels did not change significantly at the 3-month follow up OGTT (25.8 vs. 25.6; p = 0.80). There was no significant association between GLP-1 levels and unfavorable mRS (OR 1.03, 95% CI 0.95–1.12, p = 0.50). Conclusions Endogenous GLP-1 levels in patients that recently suffered an ischemic stroke are higher than in healthy controls and remained unchanged at the 3 months follow-up, possibly indicating an elevation of the levels of GLP-1 already pre-stroke. However, no association between endogenous GLP-1 and functional outcome of stroke 3 months post stroke was found.

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The downregulation of sweet taste receptor signaling in enteroendocrine L-cells mediates 3-deoxyglucosone-induced attenuation of high glucose-stimulated GLP-1 secretion

Abstract: 3DG attenuates high glucose-stimulated GLP-1 secretion by reducing STR subunit expression and downstream signaling components.

Cited by 11 publications

References 30 publications

3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions

3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions

Greater glucagon-like peptide-1 responses to oral glucose are associated with lower central and peripheral blood pressures

GLP-1 secretion in acute ischemic stroke: association with functional outcome and comparison with healthy individuals

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