HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/E416    most recent 00331.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Hong, J. Articles by Hermansen, K. Search for Related Content PubMed PubMed Citation Articles by Hong, J. Articles by Hermansen, K.

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

¹Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus C; and ²The Molecular Endocrinology Unit, Medical Biotechnology Centre, Odense University Hospital, Odense C, Denmark

Submitted 21 July 2005 ; accepted in final form 3 October 2005

Long-term exposure to fatty acids impairs -cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on -cells. We therefore studied the prolonged impact of palmitate on -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 -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 -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-, 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 -TC1-6 cells. Stevioside was able to counteract the -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.

fatty acids; glucagon; gene expression; -TC1-6 cells