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)

The natural sweetener stevioside, which is found in the plant Stevia rebaudiana Bertoni, has been used for many years in the treatment of diabetes among Indians in Paraguay and Brazil. However, the mechanism for the blood glucose-lowering effect remains unknown. To elucidate the impact of stevioside and its aglucon steviol on insulin release from normal mouse islets and the beta-cell line INS-1 were used. Both stevioside and steviol (1 nmol/L to 1 mmol/L) dose-dependently enhanced insulin secretion from incubated mouse islets in the presence of 16.7 mmol/L glucose (P < .05). The insulinotropic effects of stevioside and steviol were critically dependent on the prevailing glucose concentration, ie, stevioside (1 mmol/L) and steviol (1 micromol/L) only potentiated insulin secretion at or above 8.3 mmol/L glucose (P < .05). Interestingly, the insulinotropic effects of both stevioside and steviol were preserved in the absence of extracellular Ca2+. During perifusion of islets, stevioside (1 mmol/L) and steviol (1 micromol/L) had a long-lasting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). To determine if stevioside and steviol act directly on beta cells, the effects on INS-1 cells were also investigated. Stevioside and steviol both potentiated insulin secretion from INS-1 cells (P < .05). Neither stevioside (1 to 100 micromol/L) nor steviol (10 nmol/L to 10 micromol/L) influenced the plasma membrane K+ adenosine triphosphate ((K+)ATP)-sensitive channel activity, nor did they alter cyclic adenosine monophosphate (cAMP) levels in islets. In conclusion, stevioside and steviol stimulate insulin secretion via a direct action on beta cells. The results indicate that the compounds may have a potential role as antihyperglycemic agents in the treatment of type 2 diabetes mellitus.
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PMID:Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. 1069 Sep 46

Extracts of leaves from the plant Stevia rebaudiana Bertoni have been used in the traditional treatment of diabetes in Paraguay and Brazil. Recently, we demonstrated a direct insulinotropic effect in isolated mouse islets and the clonal beta cell line INS-1 of the glycoside stevioside that is present in large quantity in these leaves. Type 2 diabetes is a chronic metabolic disorder that results from defects in both insulin and glucagon secretion as well as insulin action. In the present study we wanted to unravel if stevioside in vivo exerts an antihyperglycaemic effect in a nonobese animal model of type 2 diabetes. An i.v. glucose tolerance test (IVGT) was carried out with and without stevioside in the type 2 diabetic Goto-Kakizaki (GK) rat, as well as in the normal Wistar rat. Stevioside (0.2 g/kg BW) and D-glucose (2.0 g/kg BW) were administered as i.v. bolus injections in anaesthetized rats. Stevioside significantly suppressed the glucose response to the IVGT in GK rats (incremental area under the curve (IAUC): 648 +/- 50 (stevioside) vs 958 +/- 85 mM x 120 min (control); P < 0.05) and concomitantly increased the insulin response (IAUC: 51116 +/- 10967 (stevioside) vs 21548 +/- 3101 microU x 120 min (control); P < 0.05). Interestingly, the glucagon level was suppressed by stevioside during the IVGT, (total area under the curve (TAUC): 5720 +/- 922 (stevioside) vs 8713 +/- 901 pg/ml x 120 min (control); P < 0.05). In the normal Wistar rat stevioside enhanced insulin levels above basal during the IVGT (IAUC: 79913 +/- 3107 (stevioside) vs 17347 +/- 2882 microU x 120 min (control); P < 0.001), however, without altering the blood glucose response (IAUC: 416 +/- 43 (stevioside) vs 417 +/- 47 mM x 120 min (control)) or the glucagon levels (TAUC: 5493 +/- 527 (stevioside) vs 5033 +/- 264 pg/ml x 120 min (control)). In conclusion, stevioside exerts antihyperglycaemic, insulinotropic, and glucagonostatic actions in the type 2 diabetic GK rat, and may have the potential of becoming a new antidiabetic drug for use in type 2 diabetes.
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PMID:Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats. 1192 70

Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure-lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6 weeks. An intra-arterial catheter was inserted into the rats after 5 weeks, and conscious rats were subjected to arterial glucose tolerance test (2.0 g x kg(-1)) during week 6. Stevioside had an antihyperglycemic effect (incremental area under the glucose response curve [IAUC]): 985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes, (P <.05), it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside] v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05) and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234 [stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05). In addition, stevioside caused a pronounced suppression of both the systolic (135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74 +/- 1 v 83 +/- 1 mm Hg; P <.001). Bolus injections of stevioside (0.025 g x kg(-1)) did not induce hypoglycemia. Stevioside augmented the insulin content in the beta-cell line, INS-1. Stevioside may increase the insulin secretion, in part, by induction of genes involved in glycolysis. It may also improve the nutrient-sensing mechanisms, increase cytosolic long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1 (PDE1) estimated by the microarray gene chip technology. In conclusion, stevioside enjoys a dual positive effect by acting as an antihyperglycemic and a blood pressure-lowering substance; effects that may have therapeutic potential in the treatment of type 2 diabetes and the metabolic syndrome.
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PMID:Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat. 1264 78

Stevioside is present in the plant Stevia rebaudiana Bertoni (SrB). Extracts of SrB have been used for the treatment of diabetes in, for example, Brazil, although a positive effect on glucose metabolism has not been unequivocally demonstrated. We studied the acute effects of stevioside in type 2 diabetic patients. We hypothesize that supplementation with stevioside to a test meal causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients were included in an acute, paired cross-over study. A standard test meal was supplemented with either 1 g of stevioside or 1 g of maize starch (control). Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion of the test meal. Compared to control, stevioside reduced the incremental area under the glucose response curve by 18% (P =.013). The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside compared to control (P <.001). Stevioside tended to decrease glucagon levels, while it did not significantly alter the area under the insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide curves. In conclusion, stevioside reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism. Stevioside may be advantageous in the treatment of type 2 diabetes.
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PMID:Antihyperglycemic effects of stevioside in type 2 diabetic subjects. 1468 45

We have studied the effects of stevioside on the glucose and insulin metabolism in 2 models of diabetes in rats, STZ-induced diabetic rats and NIDDM diabetic rats induced by feeding with fructose. Stevioside (0.5 mg/kg), lowered the blood glucose levels in STZ-induced diabetic rats, peaking at 90 min. Stevioside administered twice daily also demonstrated dose-dependent effects in lowering the glucose levels in both diabetic rat models. Stevioside reduced the rise in glucose during glucose tolerance testing in normal rats. Stevioside dose-dependently decreased protein levels of phosphoenol pyruvate carboxykinase (PEPCK) and PEPCK mRNA after 15 days of treatment. Stevioside also reduced insulin resistance in the diabetic animals as shown by the glucose lowering effects of tolbutamide. In conclusion, stevioside was able to regulate blood glucose levels by enhancing not only insulin secretion, but also insulin utilization in insulin-deficient rats; the latter was due to decreased PEPCK gene expression in rat liver by stevioside's action of slowing down gluconeogenesis. Further studies of this agent for the treatment of diabetes appear warranted.
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PMID:Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana. 1572 17

The world witnesses an explosive increase in diabetes, demanding intensified prevention and treatment not least for the low-income population. The plant, Stevia rebaudiana Bertoni, has been used for the treatment of diabetes in traditional medicine. We have previously demonstrated that stevioside, a diterpene glycoside isolated from the plant Stevia rebaudiana Bertoni, possesses insulinotropic, glucagonostatic, antihyperglycemic, and blood pressure-lowering effects in animal studies. We have also found that a dietary supplement, Abalon, of soy protein, isoflavones, and cotyledon fiber has beneficial effects on cardiovascular risk markers in type 2 diabetes. The aim of this study was to investigate if the combination of stevioside and a dietary supplement of soy protein possesses beneficial qualities in the treatment of type 2 diabetes and the metabolic syndrome. We randomized male Zucker diabetic fatty rats into 4 groups and fed them the different test diets for 10 weeks: (A) standard carbohydrate-rich laboratory diet (chow), (B) chow+stevioside (0.03 g/kg body weight [BW] per day), (C) 50% soy (Abalon)+50% chow (adjusted for vitamins and minerals), and (D) 50% soy (Abalon)+50% chow+stevioside 0.03 g/kg BW per day. We measured plasma glucose, blood pressure, weight, and food intake once weekly. The animals were equipped with an intra-arterial catheter, and at week 10, the conscious rats underwent an intra-arterial glucose tolerance test (2.0 g/kg BW). Stevioside exerts beneficial effects in type 2 diabetic Zucker diabetic fatty rats, that is, lowers blood glucose (area under the glucose curve [AUC(30min)]: group A vs B, a 19% reduction; and group C vs D, a 12% reduction; P<.001). We did not detect any effect on insulin or glucagon responses. After 2 weeks of treatment, a decrease in the systolic blood pressure was observed in the stevioside-treated groups (P<.01). Abalon had beneficial effects on cardiovascular risk markers, that is, (1) lowers total cholesterol (P<.01), (2) reduces triglycerides (P=.01), and (3) reduces free fatty acids (P<.001). The combination of stevioside and soy supplementation appears to possess the potential as effective treatment of a number of the characteristic features of the metabolic syndrome, that is, hyperglycemia, hypertension, and dyslipidemia. A long-term human study of the concept in type 2 diabetic subjects is needed to verify these promising results in animal diabetes.
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PMID:Preventive effects of a soy-based diet supplemented with stevioside on the development of the metabolic syndrome and type 2 diabetes in Zucker diabetic fatty rats. 1612 30

Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We also investigated whether the antihyperglycemic agent stevioside was able to counteract these effects of palmitate. Clonal alpha-TC1-6 cells were cultured with palmitate in the presence or absence of stevioside. After 72 h, we evaluated glucagon secretion, glucagon content, triglyceride (TG) content, and changes in gene expression. Glucagon secretion was dose-dependently increased after 72-h culture, with palmitate at concentrations >or=0.25 mM (P< 0.05). Palmitate (0.5 mM) enhanced TG content of alpha-cells by 73% (P< 0.01). Interestingly, stevioside (10(-8) and 10(-6) M) reduced palmitate-stimulated glucagon release by 22 and 45%, respectively (P< 0.01). There was no significant change in glucagon content after 72-h culture with palmitate and/or stevioside. Palmitate increased carnitine palmitoyltransferase I (CPT I) mRNA level, whereas stevioside enhanced CPT I, peroxisome proliferator-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (P<0.05). In conclusion, long-term exposure to elevated fatty acids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes.
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PMID:Stevioside counteracts the alpha-cell hypersecretion caused by long-term palmitate exposure. 1620 36

The sulfonylurea glyburide (GB) is one of the most frequently used drugs in diabetes treatment. Long-term pretreatment with GB causes elevated basal insulin secretion (BIS) and decreased glucose-stimulated insulin secretion (GSIS). These characteristics may play an important role for the development of hypoglycemia and secondary failure. Stevioside (SVS), a substance extracted from leaves of Stevia rebaudiana Bertoni, enhances GSIS but not BIS. The aim of the present study was to clarify whether 24-hour exposure of isolated mouse islets to GB causes dose-dependent decrease in the GSIS and whether it is possible to counteract this desensitization by SVS. We also tested the impact of the incretin glucagon-like peptide-1 (GLP-1) on the GB-induced desensitization. After 24-hour preincubation with GB in combination with SVS or GLP-1, we measured the basal and glucose-stimulated insulin responses and the total islet insulin content. We also determined the fold change in gene expression of pancreatic and duodenal homeobox 1 and glucose transporter isoform 2. After 24-hour preincubation in 11.1 mmol/L glucose, GB (10(-11)-10(-3) mol/L) caused a dose-dependent decrease in GSIS (16.7 mmol/L glucose) (P < .001). GB (10(-7) mol/L) pretreatment elevated BIS, but neither SVS (10(-7) mol/L) nor GLP-1 (10(-7) mol/L) could reverse this. Interestingly, the GB-induced desensitization of GSIS was counteracted by both SVS (P < .05) and GLP-1 (P < .05). SVS reversed the decrease in insulin content caused by GB pretreatment (P < .05). GB pretreatment did not change gene expression of pancreatic and duodenal homeobox 1 nor glucose transporter isoform 2, whereas SVS significantly up-regulated the expression of both genes by more than 2-fold (P < .05). Our results showed that SVS in combination with GB did not reverse GB-induced increase in BIS, whereas both SVS and GLP-1 counteracted GB-induced desensitization of GSIS. SVS is able to counteract the desensitizing effects of GB and may be a putative new drug candidate for the treatment of type 2 diabetes mellitus.
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PMID:Stevioside counteracts the glyburide-induced desensitization of the pancreatic beta-cell function in mice: studies in vitro. 1714 43

This study investigated the potential of stevioside to prevent oxidative DNA damage in the liver and kidney of type 2 diabetes mellitus (T2DM) using high fat-low streptozocin rat model. Rats were treated daily with 12.5, 25 and 50 mg/kg stevioside orally for 21 days. Levels of biomarkers of T2DM, lipid profile and oxidative stress were assayed spectrophotometrically. The DNA ladder assay method was used to assess DNA fragmentation in the liver and kidney while computational analysis was used to predict the mechanisms of antidiabetic properties of stevioside. Stevioside significantly (p < 0.05) decreased the levels of plasma glucose, insulin, dipeptidyl peptidase IV and activities of kidney angiotensin converting enzyme. Stevioside significantly reduced oxidative stress by decreasing the levels of lipid peroxidation and nitric oxide in the liver and kidney; thereby, reducing the extent of DNA fragmentation in the liver and kidney of the diabetic rats. The in silico analysis showed that the ability of stevioside to exert these effects is linked to its inhibition of beta-adrenergic receptor kinase and G-protein-coupled receptor kinase. The results of this study suggest that the prevention of DNA fragmentation may be an additional benefit of the use of stevioside in the management of T2DM.
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PMID:Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats. 2987 71