Stevioside counteracts the α-cell hypersecretion caused by long-term palmitate exposure

Abstract

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.

Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells

“…Contrary to the situation found in β-cells, long-term exposure to palmitate or oleate increases glucagon secretion of mouse and rat islets and αTC1-cells (Hong et al 2006(Hong et al , 2007 and abolishes the glucagonostatic effect of glucose (Collins et al 2008;Dumonteil et al 2000). These effects raise the question whether elevated plasma FFA levels may aggravate the hyperglucagonemia associated with type 2 diabetes.…”

The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion

“…Stevioside, the parent compound of isosteviol, protects both α and β-cells against the effects of palmitate Hong et al, 2006). Furthermore, Hong et al (2006) suggested that the presence of palmitate contributes to stevioside's protective effects because in the presence of palmitate, stevioside enhances the gene expression of stearoyl-CoA desaturase (SCD). SCD converts palmitate to palmitoleate which is protective against apoptosis.…”

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

“…In this context, it is interesting that plasma glucagons were decreased by 29% during the IAGTT in the stevioside-treated groups compared with the control group, and that the effect seems to be further enhanced when soy protein is added, where we found a lowering effect of 49%. Similarly, stevioside has recently been shown to reduce the palmitate-stimulated glucagon release from α-cells [28]. Clearly, SPI alone had no significant effect on glucagons.…”