October 2, 2016: Excessive sugar consumption — specifically the sugar fructose such as in soda — has been linked to a rise in metabolic disease worldwide, a study has found.
Some investigators contend that commonly consumed amounts of sugar do not contribute to this epidemic. While others are convinced that excessive sugar ingestion is a major cause.
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"There is still significant controversy as to whether sugar consumption is a major contributor to the development of diabetes," said senior author Mark Herman, Assistant Professor at Duke University.
However, "the study reveals a specific mechanism by which consuming fructose in large amounts, such as in soda, can cause problems", Herman added.
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Insulin is a key hormone that regulates blood glucose after eating. Insulin resistance, when the body's metabolic tissues stop responding normally to insulin, is one of the earliest detectable changes in the progression to diabetes.
The likely cause of insulin resistance may not be the build-up of fat in the liver, as commonly believed, but may be caused by excess sugar in the liver that activates a molecular factor known as carbohydrate-responsive element-binding protein, or ChREBP.
ChREBP may then contribute to the development of both fatty liver and increased glucose production, the researchers said.
The ChREBP protein is found in several metabolic organs in mice, humans and other mammals.
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"We found that no matter how much insulin the pancreas made, it couldn't override the processes started by this protein, ChREBP, to stimulate glucose production. This would ultimately cause blood sugar and insulin levels to increase, which over time can lead to insulin resistance elsewhere in the body," Herman explained.
To test their hypothesis, researchers studied mice that were genetically altered so their liver insulin signalling pathways were maximally activated — in other words, their livers should not have been able to produce any glucose.
The researchers found that even in these mice, eating fructose triggered ChREBP-related processes in the liver, causing it to make more and more glucose, despite insulin signals telling it to stop.
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Previous studies have reported that high fructose diets can cause multiple metabolic problems in humans and animals, including insulin resistance and fatty liver disease.
The finding could also help scientists one day diagnose metabolic disorders earlier on, potentially allowing patients to make changes to their diets and lifestyles sooner to prevent more serious complications.
The study was published in the Journal of Clinical Investigation.