Insulin resistance in metabolic syndrome – conclusion

Association of fructose intake with features of metabolic syndrome such as insulin resistance necessitates evaluation of mechanisms via which such processes proceed. This is because the knowledge of etiology of diseases such as diabetes that arise from insulin resistance helps to better approaches in managing such diseases. For instance, implication of fructose in metabolic syndrome challenges the continued use of HFCS as a sweetener in foods and beverages. Accordingly, this paper reviewed literature to highlight the mechanisms that may explain the link between dietary fructose and insulin resistance.

Various mechanisms (see figure 2 in the appendix) may explain how insulin resistance develops in conditions of high-fructose intake. Primarily, insulin resistance in high intakes of fructose is linked to obesity-linked pathways. Since the predominant pathway of fructose metabolism bypasses the rate limiting reaction (one characterized by PFK) in the glycolytic pathway, high levels of fructose intake could result to elevated levels of lipogenesis. This leads to the accumulation of triglycerides that promote insulin resistance primarily in the visceral tissue but eventually in hepatocytes. Secondly, via obesity-related mechanisms, insulin resistance is associated with fructose-induced leptin resistance.

Other potential mechanisms linking fructose to insulin resistance are related to its promotion of uric acid synthesis. Such activity of fructose results in hyperuricemia which has been associated with various features of metabolic syndrome including insulin resistance. Potential mechanisms linking hyperuricenemia to insulin resistance are its activity that resulting to endothelial dysfunction and reduced nitric oxide generation. Nitric oxide promotes insulin activity in the cells. Another mechanism related to high biosynthesis of uric acid, has been suggested to be its direct effects on adipocytes that result in enhanced oxidative stress. Following such implication of fructose in promoting insulin resistance, reduced use of HFCS may reduce the incidence and prevalence of conditions such as obesity and type II diabetes, which have affected the quality of life  in many countries in recent decades.

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