Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues

Abstract

Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months’ supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake.

Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress

“…Namely, hepatic fatty acid profile was characterized by a higher proportion of MUFA, lower proportion of PUFA and increased oleic/stearic acid ratio (Δ9 desaturase index), regardless of stress. These results are in accordance with other animal studies using high-fructose diet [39][40][41]. In addition, it was previously demonstrated that fructose-induced increase of MUFA and decrease of PUFA in the liver were not accompanied by lipid accumulation and hepatic steatosis [39,40], but rather with increased secretion of triglycerides, as observed in the present study.…”

Role of AMPD2 in impaired glucose tolerance induced by high fructose diet

“…Baena et al reported that fructose, but not glucose, exhibited adverse effects towards insulin signaling in white adipose tissues and skeletal muscle, which were also seen in the liver [30]. Taken together with our findings, it is suggested that insulin signaling in other pathways, including the role of other insulin-sensitive tissues such as skeletal muscles and adipose tissue, may play a role in glucose metabolism, especially in the setting of a high fructose diet.…”

The Addition of Liquid Fructose to a Western-Type Diet in LDL-R−/− Mice Induces Liver Inflammation and Fibrogenesis Markers without Disrupting Insulin Receptor Signalling after an Insulin Challenge

“…Our research group has shown that liquid fructose supplementation in female rats fed a standard chow diet (two weeks to two months) induces glucose intolerance and IR [12,13,14,15]. However, unhealthy human dietary patterns frequently include not only excessive added sugars, but also excessive fat intake, particularly saturated fats [16].…”