stevioside and Hyperglycemia

Stevioside, an abundant component of Stevia rebaudiana leaf, has become well-known for its intense sweetness (250-300 times sweeter than sucrose) and is used as a non-caloric sweetener in several countries. A number of studies have suggested that, beside sweetness, stevioside along with related compounds, which include rebaudioside A (second most abundant component of S. rebaudiana leaf), steviol and isosteviol (metabolic components of stevioside) may also offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. It is of interest to note that their effects on plasma glucose level and blood pressure are only observed when these parameters are higher than normal. As steviol can interact with drug transporters, its role as a drug modulator is proposed. This review summarizes the current knowledge of the pharmacological actions, therapeutic applications, pharmacokinetics and safety of stevioside and related compounds. Although much progress has been made concerning their biological and pharmacological effects, questions regarding chemical purity and safety remain unsolved. These issues are discussed to help guide future research directions.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Carcinogens; Diterpenes, Kaurane; Diuretics; Drug Interactions; Glucosides; Humans; Hyperglycemia; Hypertension; Ion Pumps; Sweetening Agents

In diabetes, in parallel to hyperglycaemia, elevated serum lipids are also diagnosed, representing a high-risk factor for coronary heart disease and cardiovascular complications. The objective of this study was to unravel the mechanisms that underlie the potential of steviol glycosides (stevioside or rebaudioside A) administered at two doses (500 or 2500 mg/kg body weight for 5 weeks) to regulate lipid metabolism. In this paper, the expression of selected genes responsible for glucose and lipid metabolism (Glut4, Pparγ, Cebpa, Fasn, Lpl and Egr1) in the peripheral tissues (adipose, liver and muscle tissue) was determined using quantitative real-time PCR method. It was found that the supplementation of steviol glycosides affected the expression of Glut4, Cebpa and Fasn genes, depending on the type of the glycoside and its dose, as well as the type of tissue, whish in part may explain the lipid-regulatory potential of steviol glycosides in hyperglycaemic conditions. Nevertheless, more in-depth studies, including human trials, are needed to confirm these effects, before steviol glycosides can be used in the therapy of type 2 diabetes.

Topics: Diabetes Mellitus, Type 2; Gene Expression; Glycosides; Humans; Hyperglycemia; Lipid Metabolism; Stevia

Diabetes mellitus is a chronic disease characterized by abnormal carbohydrate, lipid and protein metabolism due to a lack of insulin or reduced target cell sensitivity to insulin. Stevia rebaudiana is an important source of biochemically active substances with proven anti-diabetic effect. The aim of this study was to determine anti-diabetic effects of the low dose of stevioside in NMRI Haan mice. Aqueous stevioside solution (20mg/kg body weight) was administered by oral route of administration. Anti-diabetic effect of stevioside was estimated by oral glucose tolerance test, adrenaline test after a 10day stevioside treatment, and alloxan induced hyperglycaemia in mice (two experimental groups, 10day stevioside treatment before and after alloxan administration). Aqueous stevioside solution prevented significant increase in glycaemia in oral glucose tolerance test (9.22±1.13 to 9.85±1.32mmol/l, P<0.05), and not in adrenaline test. Significant difference in glycaemia was detected in mice pre-treated with saline and stevioside in alloxan induced hyperglycaemia (saline 23.32±2.14, stevioside 14.70±4.95mmol/l, P<0.05). In mice pre-treated with stevioside, smallest β cells loss was found compared to other alloxan treated groups. Preserved normal cytoarchitectonic arrangement in islets was detected. Based on the given results we presume there exist a potential therapeutic use of low dose stevioside in diabetes.

Topics: Alloxan; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diterpenes, Kaurane; Glucose Tolerance Test; Glucosides; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Mice; Phytotherapy; Plant Extracts; Stevia

The aim of this study was to investigate influence of the preparation based on barley and brewer's yeast extracts with chromium (BBCr) and stevioside (S) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. The animals were divided into three groups: glucose 500 mgkg(-1) (I); adrenalin 0.2 mgkg(-1)(II) and alloxan 100 mg kg(-1) (III) and into subgroups according to the substance they received: stevioside 20 mg kg(-1) (I-S, II-S, III-S); BBCr 750 mg kg(-1)(I-BBCr, II-BBCr, III-BBCr) and saline 1 ml/100g (III-placebo). Glycaemia was measured before and after 7-day treatment with stevioside or BBCr in the following conditions: fasting, 30 min after glucose load (I) or 45 min after adrenaline load (II). In group III glycaemia was measured before and after 12-day treatment with S, BBCr or placebo and alloxan application (7th, 8th and 10th days of treatment ). BBCr significantly reduced fasting glycaemia in I and II groups and glycaemia values after the glucose load (I-BBCr: 9.20 ± 0.61 vs. 7.42 ± 0.59 mmol/L, p = 0.01). Stevioside significantly reduced glycaemia after the adrenalin load (II-S: 13.45 ± 0.71 vs. 11.65 ± 1.19 mmol/L; p = 0.03). In the III-BBCr glycaemia values did not indicate the development of alloxan-induced diabetes and were significantly lower than in the III-placebo (8.6 ± 3.16 vs. 18.8 ± 5.53 mmol/L; p < 0.05). In conclusion, BBCr caused a significant decrease of fasting glycaemia, significant reduction of glycaemia after glucose load and prevented onset of alloxan-induced diabetes. Stevioside caused the decrease of adrenalin-induced hyperglycaemia.

Topics: Alloxan; Animals; Blood Glucose; Chromium; Diabetes Mellitus, Experimental; Disease Models, Animal; Diterpenes, Kaurane; Epinephrine; Fasting; Female; Glucose; Glucosides; Hordeum; Hyperglycemia; Hypoglycemic Agents; Male; Mice; Mice, Inbred Strains; Plant Extracts; Saccharomyces cerevisiae

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.

Topics: Animals; Area Under Curve; Diabetes Mellitus, Type 2; Disease Models, Animal; Diterpenes; Diterpenes, Kaurane; Glucagon; Glucose; Glucose Tolerance Test; Glucosides; Hyperglycemia; Hypoglycemic Agents; Injections, Intravenous; Insulin; Male; Phytotherapy; Plant Extracts; Rats; Rats, Inbred Strains; Rats, Wistar; Terpenes