Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the prevalence of obesity, non-nutritive sweeteners (NNS) have been widely used as sugar substitutes as they deliver a sweet taste without excessive caloric load. However, it is increasingly recognized that NNS are not inert compounds and may cause long-term metabolic perturbations. Endoplasmic reticulum (ER) stress has emerged as a critical link in the development of obesity and type 2 diabetes. In this study, we investigated the effects of NNS found in common diet beverages (i.e., sucralose, aspartame, acesulfame potassium) and a natural sweetener (i.e., rebaudioside A) on ER stress in the hypothalamic cell line mHypoE-N43/5 in vivo and on axonal outgrowth ex vivo. Sucralose, aspartame, and acesulfame potassium caused elevated ER stress gene expression in mHypoE-N43/5 cells, with sucralose and acesulfame potassium having the most potent effect. Moreover, acesulfame potassium treatment reduced axon outgrowth from arcuate nucleus explants and this effect was attenuated with the ER stress-relieving drug tauroursodeoxycholic acid. Furthermore, sucralose induced cytotoxicity and acesulfame potassium increases caspase3/7 activity at high concentrations in mHypoE-N43/5 cells. In contrast, rebaudioside A only had moderate effects on hypothalamic ER stress and no adverse effects on axon outgrowth, cytotoxicity, or caspase3/7 activity. Together, our data reveal that commonly consumed NNS cause cellular stress in hypothalamic cells disrupting axon outgrowth and that these biological alterations are not seen with rebaudioside A. These data provide biological plausibility for some NNS to adversely impact metabolic health and identifies rebaudioside A as a sweetener with lower detrimental biological impact on hypothalamic cells.
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PMID:Non-nutritive Sweeteners Induce Hypothalamic ER Stress Causing Abnormal Axon Outgrowth. 3192 Sep 85

Dietary sugar has been largely related to the onset of metabolic diseases such as type 2 diabetes and obesity, among others. The growing awareness on the close relationship between the dietary habits and this health disturbance has encouraged the development of new beverages using alternative sweeteners that could contribute to combat the above referred pathophysiological disorders. To gain further insight into this issue, the present work, upon an acute dietary intervention, evaluated the urinary excretion of flavanones ingested through polyphenols-rich beverages composed of maqui berry and citrus, with the aim of establishing the highest urinary excretion rate and metabolite profiles. The functional beverages evaluated were supplemented with a range of sweeteners including sucrose (natural and high caloric), stevia (natural and non-caloric), and sucralose (artificial and non-caloric) as an approach that would allow reducing the intake of sugars and provide bioactive phenolics (flavanones). The juices developed were ingested by volunteers (n = 20) and the resulting flavanones and their phase II metabolites in urine were analyzed by Ultra-High Performance Liquid Chromatography ElectroSpray Ionization Mass Spectrometry (UHPLC-ESI-MS/MS). A total of 16 metabolites were detected: eriodyctiol, naringenin, and homoeriodyctiol derivatives, where peak concentrations were attained 3.5 h after beverage intake. Sucralose and stevia were the sweeteners that provided the highest urinary excretion for most compounds. Sucrose did not provide a remarkable higher elimination through urine of any compounds in comparison with sucralose or stevia. These results propose two alternative sweeteners to sucrose (sucralose and stevia), an overused, high caloric sweetener that promotes some metabolic diseases.
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PMID:Alternative Sweeteners Modify the Urinary Excretion of Flavanones Metabolites Ingested through a New Maqui-Berry Beverage. 3194 12

Sugar intake abuse is directly related with the increase of metabolic diseases such as type 2 diabetes, obesity, and insulin resistance. Along this line, the development of new beverages using alternative sweeteners could help with combatting the pathophysiological disorders associated to the consumption of sugar. To provide evidence on this issue, in the present work, the bioavailability of anthocyanins was evaluated after the acute ingestion of a new maqui-citrus-based functional beverage rich in polyphenols, and supplemented with a range of sweeteners including sucrose (natural high caloric), stevia (natural non-caloric), and sucralose (artificial non-caloric), as an approach that would allow reducing the intake of sugars while providing bioactive phenolic compounds (anthocyanins). This approach allowed the evaluation of the maximum absorption and the diversity of metabolites excreted through urine. The beverages created were ingested by volunteers (n = 20) and the resulting anthocyanin metabolites in their urine were analyzed by UHPLC-ESI-MS/MS. A total of 29 degradation metabolites were detected: Caffeic acid, catechol, 3,4-dihidroxifenilacetic acid, hippuric acid, trans-ferulic acid, 2,4,6-trihydroxybenzaldehyde, trans-isoferulic acid, and vanillic acid derivatives, where peak concentrations were attained at 3.5 h after beverage intake. Sucralose was the sweetener that provided a higher bioavailability for most compounds, followed by stevia. Sucrose did not provide a remarkably higher bioavailability of any compounds in comparison with sucralose or stevia. The results propose two sweetener alternatives (sucralose and stevia) to sucrose, an overused high calorie sweetener that promotes some metabolic diseases.
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PMID:Anthocyanin Metabolites in Human Urine after the Intake of New Functional Beverages. 3196 36