Sunday, 22 July 2007

Stevioside counteracts α-cell hypersecretion

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

Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E416-22.
DOI 10.1152/ajpendo.00331.2005 (pdf)

Hong J, Chen L, Jeppesen PB, Nordentoft I, Hermansen K

Long-term exposure to fatty acids impairs β-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on α-cells. We therefore studied the prolonged impact of palmitate on α-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 α-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 ≥0.25 mM (P < 0.05). Palmitate (0.5 mM) enhanced TG content of α-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-γ, 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 α-TC1-6 cells. Stevioside was able to counteract the α-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.

(First published October 4, 2005)

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