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Journal ArticleDOI

Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review

12 Nov 2013-Evidence-based Complementary and Alternative Medicine (Hindawi Publishing Corporation)-Vol. 2013, pp 718049-718049

AbstractInsulin resistance is a key factor in metabolic disorders like hyperglycemia and hyperinsulinemia, which are promoted by obesity and may later lead to Type II diabetes mellitus. In recent years, researchers have identified links between insulin resistance and many noncommunicable illnesses other than diabetes. Hence, studying insulin resistance is of particular importance in unravelling the pathways employed by such diseases. In this review, mechanisms involving free fatty acids, adipocytokines such as TNFα and PPARγ and serine kinases like JNK and IKKβ, asserted to be responsible in the development of insulin resistance, will be discussed. Suggested mechanisms for actions in normal and disrupted states were also visualised in several manually constructed diagrams to capture an overall view of the insulin-signalling pathway and its related components. The underlying constituents of medicinal significance found in the Stevia rebaudiana Bertoni plant (among other plants that potentiate antihyperglycemic activities) were explored in further depth. Understanding these factors and their mechanisms may be essential for comprehending the progression of insulin resistance towards the development of diabetes mellitus.

Topics: Stevia rebaudiana (65%), Insulin resistance (62%), Hyperinsulinemia (56%), Diabetes mellitus (51%)

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Citations
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Journal ArticleDOI

[...]

08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

30,199 citations


Journal ArticleDOI
TL;DR: The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance.
Abstract: Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance.

508 citations


Cites background from "Potential Roles of Stevia rebaudian..."

  • ...The mechanisms by which Stevia leaves and its steviol glycosides exert a marked antidiabetic effect have been intensively studied [16]....

    [...]


03 Jul 2015
TL;DR: The journal policy is to publish work deemed by peer reviewers to be a coherent and sound addition to scientific knowledge and to put less emphasis on interest levels, provided that the research constitutes a useful contribution to the field.
Abstract: Journal of Pharmaceutical and Biological Sciences (An international peer-reviewed Bi-monthly journal) is a peer-reviewed journal of high quality devoted to provide a platform to scientists and researchers all over the world, for the dissemination of knowledge in the field of Pharmaceutical, Biological and other allied sciences. The journal policy is to publish work deemed by peer reviewers to be a coherent and sound addition to scientific knowledge and to put less emphasis on interest levels, provided that the research constitutes a useful contribution to the field. The Journal publishes original research papers, review articles, and short communications in all aspects of Pharmacy, Biology and other allied sciences.

47 citations


Journal ArticleDOI
TL;DR: In order to identify noxious synthetic compounds in the environment out of the thousands of chemicals that are currently in use, tools and models from toxicology should be adopted (e.g., functional high throughput screening methods, zebrafish-based assays).
Abstract: The “chemical obesogen” hypothesis conjectures that synthetic, environmental contaminants are contributing to the global epidemic of obesity. In fact, intentional food additives (e.g., artificial sweeteners and colors, emulsifiers) and unintentional compounds (e.g., bisphenol A, pesticides) are largely unstudied in regard to their effects on overall metabolic homeostasis. With that said, many of these contaminants have been found to dysregulate endocrine function, insulin signaling, and/or adipocyte function. Although momentum for the chemical obesogen hypothesis is growing, supportive, evidence-based research is lacking. In order to identify noxious synthetic compounds in the environment out of the thousands of chemicals that are currently in use, tools and models from toxicology should be adopted (e.g., functional high throughput screening methods, zebrafish-based assays). Finally, mechanistic insight into obesogen-induced effects will be helpful in elucidating their role in the obesity epidemic as well as preventing and reversing their effects.

35 citations


Journal ArticleDOI
TL;DR: The obtained results strongly suggest that the effect of environmental cues on steviol glycosides contents and transcription of corresponding biosynthetic genes in S. rebaudiana is significant.
Abstract: Plant growth and secondary metabolism are commonly regulated by external cues such as light, temperature and water availability. In this study, the influences of low and high temperatures, dehydration, photoperiods, and different growing stages on the changes of steviol glycosides (SGs) contents and transcription levels of fifteen genes involved in SGs biosynthesis of Stevia rebaudiana Bertoni were examined using HPLC and RT-PCR. The observations showed that the transcript levels of all the fifteen genes were maximum under 25 °C treatment, and the transcription of SrDXS, SrDXR, SrMCT, SrCMK, SrMDS, SrHDS, SrHDR, SrIDI, SrGGDPS, SrCPPS1, SrUGT85C2 and SrUGT76G1 were restrained both in low temperature (15 °C) and high temperature (35 °C). Most genes in SGs biosynthesis pathway exhibited down-regulation in dehydration. To elucidate the effect of photoperiods, the plants were treated by different simulated photoperiods (8 L/16 D, 1 0L/14 D, 14 L/10 D and 16 L/8 D), but no significant transcription changes were observed. In the study of growing stages, there were evident changes of SGs contents, and the transcript levels of all the fifteen genes were minimal in fast growing period, and exhibited evident increase both in flower-bud appearing stage and flowering stage. The obtained results strongly suggest that the effect of environmental cues on steviol glycosides contents and transcription of corresponding biosynthetic genes in S. rebaudiana is significant. It is worth to study deeply.

30 citations


Cites background from "Potential Roles of Stevia rebaudian..."

  • ...rebaudiana extract on anticariogenic, antineoplastic, antihypertensive, anti-inflammatory and antihyperglycemic were reported by many scientific literatures, and the antihyperglycemic effect is the most reported (Aranda-Gonzalez et al., 2014; Mohd-Radzman et al., 2013)....

    [...]

  • ...The effects of the S. rebaudiana extract on anticariogenic, antineoplastic, antihypertensive, anti-inflammatory and antihyperglycemic were reported by many scientific literatures, and the antihyperglycemic effect is the most reported (Aranda-Gonzalez et al., 2014; Mohd-Radzman et al., 2013)....

    [...]


References
More filters

Journal ArticleDOI

[...]

08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

30,199 citations


"Potential Roles of Stevia rebaudian..." refers result in this paper

  • ...Such findings concur with the results of other studies of Type 1 diabetes, modelled by streptozotocin-induced diabetic rats, inwhich phenolic compounds prevented several diabetic complications [45]....

    [...]


01 Jan 2008
Abstract: The existing reviews of massage therapy (MT) research are either limited to infants, adults, or were conducted prior to the publication of the most recent studies using pediatric samples. Randomized controlled trials (RCTs) of pediatric MT are reviewed. A literature search yielded 24 RCTs of pediatric MT, defined as the manual manipulation of soft tissue intended to promote health and well-being in recipients between 2 and 19 years of age. Because RCTs of pediatric MT varied considerably in the amount and types of data reported, quantitative and narrative review methods were both used. Singledose and multiple-dose effects were examined separately. Among single-dose effects, significant reductions of state anxiety were observed at the first session (g 1⁄4 0.59, P < 0.05) and the last session (g 1⁄4 1.10, P < 0.01) of a course of treatment. Effects for salivary cortisol (g 1⁄4 0.28), negative mood (g 1⁄4 0.52) and behavior (g 1⁄4 0.37) were non-significant. Three of eleven multiple-dose effects were statistically significant. These were trait anxiety (g 1⁄4 0.94, P < 0.05), muscle tone (g 1⁄4 0.90, P< 0.01) and arthritis pain (g1⁄4 1.33, P< 0.01). Results of studies not permitting effect size calculation were judged to be generally consistent with quantitative results. MT benefits pediatric recipients, though not as universally as sometimes reported. Numerous weaknesses endemic to MT research (e.g. low statistical power, frequent failure to report basic descriptive statistics) are identified, and recommendations for future pediatric MT research are discussed.

2,210 citations


Journal ArticleDOI
13 Apr 2006-Nature
TL;DR: A genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-α and the other with the glucocorticoid dexamethasone, suggests that reactive oxygen species levels are increased in both models, and increased ROS levels are an important trigger for insulin resistance in numerous settings.
Abstract: Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.

2,097 citations


Journal ArticleDOI
09 Oct 1997-Nature
TL;DR: Results indicate that TNF-α is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action.
Abstract: Obesity is highly associated with insulin resistance and is the biggest risk factor for non-insulin-dependent diabetes mellitus. The molecular basis of this common syndrome, however, is poorly understood. It has been suggested that tumour necrosis factor (TNF)-alpha is a candidate mediator of insulin resistance in obesity, as it is overexpressed in the adipose tissues of rodents and humans and it blocks the action of insulin in cultured cells and whole animals. To investigate the role of TNF-alpha in obesity and insulin resistance, we have generated obese mice with a targeted null mutation in the gene encoding TNF-alpha and those encoding the two receptors for TNF-alpha. The absence of TNF-alpha resulted in significantly improved insulin sensitivity in both diet-induced obesity and that resulting for the ob/ob model of obesity. The TNFalpha-deficient obese mice had lower levels of circulating free fatty acids, and were protected from the obesity-related reduction in the insulin receptor signalling in muscle and fat tissues. These results indicate that TNF-alpha is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action.

2,078 citations


Journal ArticleDOI
TL;DR: It is demonstrated that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.
Abstract: To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.

1,433 citations