A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats

Abstract

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-1/2) in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days) induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05). There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 ± 4% (P<0.05) in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-1/2) phosphorylation, to 83 ± 5% (P<0.05) in liver and to 77 ± 4% (P<0.05) in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding.

Original article High fructose solution induces neuronal loss in the nucleus of the solitary tract of rats

“…In accordance with the present results, Van der Borght et al, Ueno et al and Axelsen et al [5,29,30] showed that consumption of fructose could not affect the insulin, free fatty acid and glucose lev els in fasting state. The controversial findings are reported as well [4,7,2729,32].…”

“…As listed earlier, different admin istration routes and different species of animals may explain the controversy observed [6,21,29].…”

Produção de concentrados de frutose por inulinases de Penicillium janczewskii e atividade sobre o nível de glicose plasmática em ratos diabéticos

“…Os resultados obtidos concordam com dados da literatura que mostram que frutose em baixas concentrações pode reduzir níveis de glicose do sangue [10]. Recentemente foi verificado que animais submetidos a dietas com alto teor de frutose apresentaram aumento do nível de triglicérides plasmáticos [30], alertando para o fato de que a utilização de concentrados de frutose em dietas alimentares de diabéticos precisa ser dosada e estar sob vigilância.…”

Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical Exercise on the Hepatic Metabolism

“…This mechanism of hepatic insulin resistance perpetuates the sign of hepatic 5 of 20 gluconeogenesis, leading to a marked increase in blood glucose and contributing to weight gain [14,38]. In 2000, Ueno and collaborators (2000) observed that insulin signalling was reduced by nearly 72% in the hepatic tissue of rodents exposed to a fructose-rich diet for 28 days [39]. In addition to inducing hepatic insulin resistance, activation of JNK-1 activates transcription factor 1 (AP-1).…”