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A single enzyme promotes the obesity-induced oxidative stress in the pancreatic cells that leads to pre-diabetes and diabetes, scientists have found. The action of the enzyme 12-LO is the last step in the production of certain small molecules that harm the cell, according to a team from Indiana University School of Medicine, Indianapolis. The findings will enable the development of drugs that can interfere with this enzyme, preventing or even reversing diabetes, researchers said.
Diabetes results when the pancreas fails to produce sufficient insulin to remove sugar from the blood. 'We surmised that when individuals eat high fat foods and become overweight, the beta cells of their pancreases fail to produce sufficient insulin,' said principal investigator Raghavendra Mirmira.
In earlier studies, the researchers and their collaborators at Eastern Virginia Medical School showed that 12-LO (which stands for 12-lipoxygenase) is present in these cells only in people who become overweight. The harmful small molecules resulting from 12-LO's enzymatic action are known as HETEs, short for hydroxyeicosatetraenoic acid.
HETEs harm the mitochondria, which then fail to produce sufficient energy to enable the pancreatic cells to manufacture the necessary quantities of insulin. The investigators genetically engineered mice that lacked the gene for 12-LO exclusively in their pancreas cells. Mice were either fed a low-fat or high-fat diet. Both the control mice and the knockout mice on the high fat diet developed obesity and insulin resistance.
The investigators also examined the pancreatic beta cells of both knockout and control mice, using both microscopic studies and molecular analysis. Those from the knockout mice were intact and healthy, while those from the control mice showed oxidative damage, demonstrating that 12-LO and the resulting HETEs caused the beta cell failure.
'Our research is the first to show that 12-LO in the beta cell is the culprit in the development of pre-diabetes, following high fat diets,' said Mirmira. 'Our work also lends important credence to the notion that the beta cell is the primary defective cell in virtually all forms of diabetes and pre-diabetes,' he said.
The research was published in the journal Molecular and Cellular Biology.
Here are some tips to prevent diabetes
1. Get your sugar levels checked: A lot of people have prediabetes (fasting sugar: 100-125 mg/dl) and are totally clueless about it. A blood sugar test will help you to understand whether you're prediabetic and what are your chances of developing diabetes. If you get diagnosed with prediabetes, then you can take the right steps and prevent it from transforming into irreversible diabetes. Here are things you should know about prediabetes.
2. Change your lifestyle: Sometimes, small changes can make a huge difference. Lifestyle intervention for preventing diabetes is the best example for this. Several studies on diabetes prevention programme have proved that diabetes can be prevented effectively by giving up sedentary lifestyle and adopting healthier changes. Read more about sedentary lifestyle and diabetes risk.
3. Eat healthy: Eat a healthy diet that has low calories, especially low saturated fats. Trials have shown that fat intake should not exceed 30 percent of the total calorie intake, whereas saturated fats should be restricted to just 10 percent. Include more of vegetables, fresh fruits, whole grains, dairy products and sources of omega 3 fats. Also, increase your fibre intake.
With inputs from PTI
Photo source: Getty images
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