QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services 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 Google Scholar Google Scholar Articles by Wei, Y. Articles by Pagliassotti, M. J. Search for Related Content PubMed PubMed Citation Articles by Wei, Y. Articles by Pagliassotti, M. J.

---

Biochemical and Molecular Actions of Nutrients

Fructose Selectively Modulates c-jun N-Terminal Kinase Activity and Insulin Signaling in Rat Primary Hepatocytes^1,2

Colorado State University, Department of Food Science and Human Nutrition, Fort Collins, CO 80523

³To whom correspondence should be addressed. E-mail: pagliasm{at}cahs.colostate.edu.

Fructose is a unique nutrient, due in part to its selective metabolism in the liver. Diets enriched in fructose or sucrose induce a hepatic stress response characterized by activation of c-jun N-terminal kinase. The aim of this study was to examine the regulation of c-jun N-terminal kinase by fructose in rat primary hepatocytes. Fructose was provided to rat primary hepatocytes using a fructose regenerating system, consisting of inulin and inulinase. This system provides a more physiologic delivery of fructose and avoids large disturbances in hepatocyte ATP concentrations. Fructose delivery increased c-jun N-terminal kinase activity and serine 307 phosphorylation of insulin receptor substrate-1 and reduced tyrosine phosphorylation of insulin receptor substrate-1. Activation of c-jun N-terminal kinase was maximal at a fructose concentration of 0.6 mmol/L. Fructose delivery did not increase the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal regulated kinase, c-jun, or activating transcription factor-2, the latter 2 downstream nuclear targets of c-jun N-terminal kinase. However, fructose delivery increased the phosphorylation of mitogen-activated protein kinase kinase-7 (MKK7), an upstream activator of c-jun N-terminal kinase, and the association of c-jun N-terminal kinase with c-jun N-terminal kinase-interacting protein-1, a scaffold protein that can sequester protein signaling complexes in the cytosol. These data suggest that fructose may selectively activate c-jun N-terminal kinase via regulation of MKK7 and scaffold proteins.

KEY WORDS: • rats • liver • fructose • stress