Author:
Wei Yuren,Wang Dong,Moran Gretchen,Estrada Andrea,Pagliassotti Michael J
Abstract
Abstract
Background
Fructose produces hepatic insulin resistance in humans and animals. We have proposed that the selective metabolism of fructose by the liver can, under conditions of elevated fructose delivery, inflict a metabolic insult that is localized to the hepatocyte. The present study was designed to identify potential cellular effectors of this insult.
Methods
Primary hepatocytes were incubated with 8 mM glucose and 0.12% inulin (G, n = 6) or 8 mM glucose, 0.12% inulin and 28 mU of inulinase (GF, n = 6) in the presence or absence of insulin for 0, 2, or 4 h.
Results
GF produced fructose concentrations of ~0.7 mM over the 4 h experiment. GF induced phosphorylation of MKK7 and JNK, phosphorylation of serine307 on IRS-1, and reduced tyrosine phosphorylation of IRS-1 and -2. GF increased ceramide levels and reactive oxygen species (ROS); however inhibitors of ceramide synthesis or ROS accumulation did not prevent GF-mediated changes in MKK7, JNK or IRS proteins. GF increased cellular methylglyoxal concentrations and a selective increase in methylglyoxal recapitulated the GF-induced changes in MKK7, JNK and IRS proteins.
Conclusions
We hypothesize that GF-mediated changes in stress signaling involve methylglyoxal in primary hepatocytes.
Publisher
Springer Science and Business Media LLC
Subject
Nutrition and Dietetics,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)
Reference40 articles.
1. Bleich SN, Wang YC: Consumption of sugar-sweetened beverages among adults with type 2 diabetes. Diabetes Care. 2011, 34 (3): 551-555. 10.2337/dc10-1687.
2. Malik VS, Schulze MB, Hu FB: Intake of sugar-sweetened beverages and weight gain: a systematic review. Am J Clin Nutr. 2006, 84 (2): 274-288.
3. Pagliassotti MJ, Prach PA, Koppenhafer TA, Pan DA: Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol. 1996, 271 (5 Pt 2): R1319-R1326.
4. Pagliassotti MJ, Shahrokhi KA, Moscarello M: Involvement of liver and skeletal muscle in sucrose-induced insulin resistance: dose-response studies. Am J Physiol. 1994, 266 (5 Pt 2): R1637-R1644.
5. Storlien LH, Kraegen EW, Jenkins AB, Chisholm DJ: Effects of sucrose vs. starch diets on in vivo insulin action, thermogenesis, and obesity in rats. Am J Clin Nutr. 1988, 47: 420-427.
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