Original Data

Stevioside Counteracts Beta-Cell Lipotoxicity without Affecting Acetyl CoA Carboxylase

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

Abstract

Chronic exposure to high levels of free fatty acids impairs beta-cell function (lipotoxicity). Then basal insulin secretion (BIS) is increased and glucose-stimulated insulin secretion (GSIS) is inhibited. Acetyl CoA carboxylase (ACC) acts as the sensor for insulin secretion in pancreatic beta-cells in response to glucose and other nutrients. Stevioside (SVS), a diterpene glycoside, has recently been shown to prevent glucotoxic effect by regulating ACC activity. The aim of this study was to investigate whether SVS can alleviate impaired beta-cell function by regulating ACC activity. We exposed isolated rat islets and the clonal beta-cell line, INS-1E, to palmitate concentrations of 1.0 or 0.6 mM, respectively, for a period of 24 h to 120 h. The results showed that lipotoxicity occurred in rat islets after 72 h exposure to 1.0 mM palmitate. The lipotoxicity was counteracted by 10^-6 M SVS (n = 8, p < 0.001). Similar results were obtained in INS-1E cells. Neither SVS nor palmitate had any effect on the gene expression of ACC, insulin 2, and glucose transporter 2 in INS-1E cells. In contrast, palmitate significantly increased the gene expression of carnitine palmitoyl transporter 1 (n = 6, p = 0.003). However, the addition of SVS to palmitate did not counteract this effect (n = 6, p = 1.0). During lipotoxicity, SVS did not alter levels of ACC protein, phosphorylated-ACC, ACC activity or glucose uptake. Our results showed that SVS counteracts the impaired insulin secretion during lipotoxicity in rat islets as well as in INS-1E cells without affecting ACC activity.

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Can Stevioside in Combination with a Soy-Based Dietary Supplement Be a New Useful Treatment of Type 2 Diabetes? An In Vivo Study in the Diabetic Goto-Kakizaki Rat

Per B. Jeppesen, Stig E. Dyrskog, Andreas Agger, Soren Gregersen, Michele Colombo, Jianzhong Xiao, Kjeld Hermansen

Abstract

The diterpene glycoside stevioside (SVS) and soy bean protein isolate have both been shown to have beneficial effects in diabetes treatment. As they each show different benefits we investigated whether the combination of both substances shows an improvement in the treatment of diabetes in Goto-Kakizaki (GK) rats. Over the course of 4 wk, the rats were fed with the following four test diets (n = 12 per group): 1. Standard carbohydrate-rich laboratory diet (chow), 2. chow + SVS (0.03 g/kg BW/day), 3. 80% SPI + 20% chow and 4. 80% SPI + 20 % chow + SVS (0.03 g/kg BW/day). At the end of the course conscious rats underwent an intra-arterial glucose tolerance test (IAGTT) (2.0 g glucose/kg BW). Compared to normal chow diet, stevioside in combination with SPI shows the following beneficial effects in GK rats with mild type 2 diabetes: 1. a 56% reduction in plasma glucose (p < 0.001), 2. a 118% increase in first-phase insulin (p < 0.005), 3. a 20% reduction in glucagons (p < 0.05), 4. a 28% reduction in total cholesterol (p < 0.001), 5. a 13% reduction in FFA (p < 0.01), 6. a 49% reduction in TG (p < 0.001) and 7. a 11% reduction in the systolic blood pressure (p < 0.001). In conclusion, the combination of stevioside and SPI has synergistic positive effects on the characteristic features of the metabolic syndrome, i.e. hyperglycemia, hypertension and dyslipidemia.

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