Stevioside Counteracts Beta-Cell Lipotoxicity without Affecting Acetyl CoA Carboxylase

Chen, Jianguo; Jeppesen, Per Bendix; Nordentoft, Iver; Hermansen, Kjeld

doi:10.1900/rds.2006.3.178

Cited by 11 publications

(7 citation statements)

References 53 publications

(57 reference statements)

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“…To assess if specific Stevia extract components were responsible for this protective effect, INS-1E, treated with palmitate, were exposed to stevioside only. This main stevia component has been shown to ameliorate insulin secretion in INS-1E cells exposed to palmitate or high glucose concentrations by different mechanisms [ 27 , 28 ]. However, in our study, we did not observe any evidence of protection by stevioside alone against palmitate-induced beta-cell death, suggesting that the improvement of beta-cell survival is likely due to combinations of Stevia components or the phytocomplex in toto .…”

Section: Discussionmentioning

confidence: 99%

“…These effects are generally thought to be due to steviol glycosides, the molecules that confer sweet flavor to Stevia extracts, although also the non-sweetener fraction might display insulinotropic effects [22]. More than 30 steviol glycosides have been detected in Stevia leaves [23], but the most abundant are stevioside, rebaudioside A and rebaudioside C. In literature, there are studies regarding the action of stevioside in stimulating insulin secretion, both in-vitro and invivo [24][25][26][27][28][29][30][31][32]. No data are currently available on the possible protective effects of Stevia extracts on pancreatic beta cells upon prolonged exposure to certain free fatty acids, also in relation to Stevia secondary metabolites -mainly steviol glycosides, polyphenols, and flavonoids-and their related antioxidant and ROS-scavenging activities.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

et al. 2021

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Aims Stevia rebaudiana Bertoni leaf extracts have gained increasing attention for their potential protection against type 2 diabetes. In this study, we have evaluated the possible beneficial effects of Stevia rebaudiana leaf extracts on beta-cells exposed to lipotoxicity and explored some of the possible mechanisms involved. Methods Extracts, deriving from six different chemotypes (ST1 to ST6), were characterized in terms of steviol glycosides, total phenols, flavonoids, and antioxidant activity. INS-1E beta cells and human pancreatic islets were incubated 24 h with 0.5 mM palmitate with or without varying concentrations of extracts. Beta-cell/islet cell features were analyzed by MTT assay, activated caspase 3/7 measurement, and/or nucleosome quantification. In addition, the proteome of INS-1E cells was assessed by bi-dimensional electrophoresis (2-DE). Results The extracts differed in terms of antioxidant activity and stevioside content. As expected, 24 h exposure to palmitate resulted in a significant decrease of INS-1E cell metabolic activity, which was counteracted by all the Stevia extracts at 200 μg/ml. However, varying stevioside only concentrations were not able to protect palmitate-exposed cells. ST3 extract was also tested with human islets, showing an anti-apoptotic effect. Proteome analysis showed several changes in INS-1E beta-cells exposed to ST3, mainly at the endoplasmic reticulum and mitochondrial levels. Conclusions Stevia rebaudiana leaf extracts have beneficial effects on beta cells exposed to lipotoxicity; this effect does not seem to be mediated by stevioside alone (suggesting a major role of the leaf phytocomplex as a whole) and might be due to actions on the endoplasmic reticulum and the mitochondrion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

et al. 2021

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“…We previously demonstrated that, during lipotoxicity, the glycosylated form of ISV, Stevioside, counteracts the impaired insulin secretion from both rat islets and INS-1E cells [19]. Stevioside was able to lower blood glucose in type 2 diabetic subjects [20] and in a non-obese animal model of type 2 diabetes i.e.…”

Section: Discussionmentioning

confidence: 99%

Isosteviol Has Beneficial Effects on Palmitate-Induced α-Cell Dysfunction and Gene Expression

et al. 2012

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BackgroundLong-term exposure to high levels of fatty acids impairs insulin secretion and exaggerates glucagon secretion. The aim of this study was to explore if the antihyperglycemic agent, Isosteviol (ISV), is able to counteract palmitate-induced α-cell dysfunction and to influence α-cell gene expression.Methodology/Principal FindingsLong-term incubation studies with clonal α-TC1–6 cells were performed in the presence of 0.5 mM palmitate with or without ISV. We investigated effects on glucagon secretion, glucagon content, cellular triglyceride (TG) content, cell proliferation, and expression of genes involved in controlling glucagon synthesis, fatty acid metabolism, and insulin signal transduction. Furthermore, we studied effects of ISV on palmitate-induced glucagon secretion from isolated mouse islets. Culturing α-cells for 72-h with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01) increase in glucagon secretion. Concomitantly, the TG content of α-cells increased by 78% (p<0.01) and cell proliferation decreased by 19% (p<0.05). At 18 mM glucose, ISV (10−8 and 10−6 M) reduced palmitate-stimulated glucagon release by 27% (p<0.05) and 27% (p<0.05), respectively. ISV (10−6 M) also counteracted the palmitate-induced hypersecretion of glucagon in mouse islets. ISV (10−6 M) reduced α-TC1–6 cell proliferation rate by 25% (p<0.05), but ISV (10−8 and 10−6 M) had no effect on TG content in the presence of palmitate. Palmitate (0.5 mM) increased Pcsk2 (p<0.001), Irs2 (p<0.001), Fasn (p<0.001), Srebf2 (p<0.001), Acaca (p<0.01), Pax6 (p<0.05) and Gcg mRNA expression (p<0.05). ISV significantly (p<0.05) up-regulated Insr, Irs1, Irs2, Pik3r1 and Akt1 gene expression in the presence of palmitate.Conclusions/SignificanceISV counteracts α-cell hypersecretion and apparently contributes to changes in expression of key genes resulting from long-term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with potential as a new anti-diabetic drug for the treatment of type 2 diabetes.

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“…Several in vitro studies showed that steviol glycosides can stimulate insulin secretion from isolated pancreatic islet cells, up-regulate key genes controlling insulin secretion and have effects on insulin signalling and release (Jeppesen et al, 1996(Jeppesen et al, , 2000(Jeppesen et al, , 2003Costa et al, 2003a;Xiao and Hermansen, 2005;Chen et al, 2006aChen et al, , 2006bChen et al, , 2006cNakamura et al, 2003;Yamamoto et al, 1985) as summarised in Appendix V-I.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive

2010

EFS2

114

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Steviol glycosides in the present evaluation are mixtures of steviol glycosides that comprise not less than 95% of stevioside and/or rebaudioside A. Stevioside as a sweetener was evaluated by the SCF in 1984, 1989 and 1999. JECFA reviewed the safety of steviol glycosides in 2000, 2005, 2006, 2007, and 2009 and established an ADI for steviol glycosides (expressed as steviol equivalents) of 4 mg/kg bw/day. The Panel considers that the results of toxicology studies on either stevioside or rebaudioside A are applicable for the safety assessment of steviol glycosides as both rebaudioside A and stevioside are metabolised and excreted by similar pathways, with steviol being the common metabolite for both. Considering the available toxicity data (in vitro and in vivo animal studies and some human tolerance studies), the Panel concludes that steviol glycosides, complying with JECFA specifications, are not carcinogenic, genotoxic or associated with any reproductive/developmental toxicity. The Panel establishes an ADI for steviol glycosides, expressed as steviol equivalents, of 4 mg/kg bw/day based on application of a 100‐fold uncertainty factor to the NOAEL in the 2‐year carcinogenicity study in the rat of 2.5% stevioside in the diet. This is equal to 967 mg stevioside/kg bw/day (corresponding to approximately 388 mg steviol equivalents/kg bw/day). Conservative estimates of steviol glycosides exposures both in adults and in children suggest that it is likely that the ADI would be exceeded at the maximum proposed use levels.

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Stevioside Counteracts Beta-Cell Lipotoxicity without Affecting Acetyl CoA Carboxylase

Cited by 11 publications

References 53 publications

Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

Isosteviol Has Beneficial Effects on Palmitate-Induced α-Cell Dysfunction and Gene Expression

Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive

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