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
TL;DR: In this paper, a review of 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, are discussed.
Abstract: Insulin 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.
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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 …
33,785 citations
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.
517 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]....
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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.
49 citations
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.
48 citations
TL;DR: The antiobesity, antihyperglycemic, antihypertensive, and antihyperlipidemic effects of the majority of glycosides and aqueous/alcoholic extracts from the leaves, flowers, and roots of the SR can serve as a natural and alternative treatment for diseases that are associated with metabolic syndrome, thus contributing to health promotion.
Abstract: Stevia rebaudiana (SR) is often used by the food industry due to its steviol glycoside content, which is a suitable calorie-free sweetener. Further, both in vitro and in vivo studies indicate that these glycosides and the extracts from SR have pharmacological and therapeutic properties, including antioxidant, antimicrobial, antihypertensive, antidiabetic, and anticancer. This work reviews the antiobesity, antihyperglycemic, antihypertensive, and antihyperlipidemic effects of the majority of glycosides and aqueous/alcoholic extracts from the leaves, flowers, and roots of the SR. These compounds can serve as a natural and alternative treatment for diseases that are associated with metabolic syndrome, thus contributing to health promotion.
43 citations
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TL;DR: SGs have made Stevia an important part of the medicinal world as well as the food and beverage industry and its role against diabetes is most important.
Abstract: Stevia rebaudiana, a perennial herb from the Asteraceae family, is known to the scientific world for its sweetness and steviol glycosides (SGs). SGs are the secondary metabolites responsible for the sweetness of Stevia. They are synthesized by SG biosynthesis pathway operating in the leaves. Most of the genes encoding the enzymes of this pathway have been cloned and characterized from Stevia. Out of various SGs, stevioside and rebaudioside A are the major metabolites. SGs including stevioside have also been synthesized by enzymes and microbial agents. These are non-mutagenic, non-toxic, antimicrobial, and do not show any remarkable side-effects upon consumption. Stevioside has many medical applications and its role against diabetes is most important. SGs have made Stevia an important part of the medicinal world as well as the food and beverage industry. This article presents an overview on Stevia and the importance of SGs.
139 citations
"Potential Roles of Stevia rebaudian..." refers background in this paper
...It is important to note that there are many steviol glycosides, which are compounds withmultiple carbohydrate molecules, bound to a noncarbohydrate, aglycone moiety (steviol) that can be extracted from the Stevia rebaudiana Bertoni plant, most commonly are stevioside, rebaudioside A, rebaudioside C and dulcoside, among many other available glycosides [42, 43]....
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TL;DR: The possibility that nutrient-sensing pathways can be a therapeutic target for diabetic nephropathy is discussed and future directions for research are suggested.
Abstract: The prevalence of diabetic nephropathy, a serious complication of diabetes, has been increasing worldwide. Therefore, there is an urgent need to identify a new therapeutic target to prevent diabetic nephropathy. “Nutrient-sensing” pathways are generally well conserved among eukaryotes. Accumulating evidence indicates that alteration of nutrient-sensing pathways and subsequent impairment of cell function in insulin-sensitive organs of mammals are involved in the pathogenesis of type 2 diabetes. According to recent reports, nutrient-sensing in the kidney also seems to be altered under diabetic conditions. In this review, we discuss the possibility that nutrient-sensing pathways can be a therapeutic target for diabetic nephropathy and suggest future directions for research.
Each cell has the ability to recognize and specifically respond to nutrient fuel substrates, such as glucose, lipids, and amino acids, to ensure their efficient use. These nutrient-sensing pathways appear critical for cellular homeostasis, for coping with starvation, and making the most of nutrient abundance. These pathways also represent important regulators of cell growth and proliferation, motility, mitochondrial function, autophagy, and survival (1–4).
Nutrient sensing is highly conserved across eukaryotic species. These pervasive regulatory pathways use posttranslational modifications of target proteins to link substrate availability to cellular homeostasis and stress responses (1–4). The best known of these pathways include the mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and the sirtuins (SIRT). Under low-energy conditions, AMPK and SIRT are activated by increases in intracellular AMP and NAD+ levels, respectively (1,2). In excessive nutrient conditions, mTOR is activated (3,4).
Each of these nutrient-sensing pathways has been implicated in the pathogenesis of obesity and diabetes, including actions on β-cell, adipocyte, hepatic and skeletal muscle metabolism, and the central regulation of nutrition (1–4). However, the same pathways may also be directly relevant to …
133 citations
TL;DR: It is suggested that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects.
Abstract: The aim of this study was to evaluate lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes, and then to establish whether moderate doses of nonenzymatic antioxidant vitamin E play a role in the antioxidant defence system in diabetic pregnant rats and their offspring. The study group consisted of 30 normal female Wistar rats, which were given a single dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the diabetic animals were divided into two matched groups: the first supplemented with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking vitamine E. Controls consisted of 15 pregnant rats. On the first day after delivery, the rats were decapitated and homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats were smaller than the healthy ones and serum glucose concentration was markedly higher in the diabetic animals. MDA levels were significantly increased, whereas GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their offspring in comparison to the control grouop. In the animals supplemented with α-tocopherol, MDA concentrations were significantly lower, GSH content and SOD activities were markedly elevated most tissues studied, whereas GPx remained unchanged. We conclude that, by monitoring the activity of selected scavenging enzymes, information on ongoing biological oxidative stress and thereby on the fetus/neonate status may be obtained. Our results suggest that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects.
121 citations
TL;DR: The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic diabetes.
Abstract: Based on the phenotypes of knockout mice and cell lines, as well as pathway-specific analysis, the insulin receptor substrates IRS-1, IRS-2, IRS-3, and IRS-4 have been shown to play unique roles in insulin signal transduction. To investigate possible functional complementarity within the IRS family, we generated mice with double knockout of the genes for IRS-1/IRS-3 and IRS-1/IRS-4. Mice with a combined deficiency of IRS-1 and IRS-4 showed no differences from Irs1−/− mice with respect to growth and glucose homeostasis. In contrast, mice with a combined deficiency of IRS-1 and IRS-3 developed early-onset severe lipoatrophy associated with marked hyperglycemia, hyperinsulinemia, and insulin resistance. However, in contrast to other models of lipoatrophic diabetes, there was no accumulation of fat in liver or muscle. Furthermore, plasma leptin levels were markedly decreased, and adenovirus-mediated expression of leptin in liver reversed the hyperglycemia and hyperinsulinemia. The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1−/−/Irs3−/− double knockout mouse as a novel model of lipoatrophic diabetes.
120 citations
TL;DR: The role of beta-cell function is reviewed, as well as the role of ectopic fat accumulation and insulin resistance in the development of type 2 diabetes in populations with a high prevalence of T2DM.
120 citations