Fatty food 'trigger' for diabetes

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Fatty food 'trigger' for diabetes

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Details: Parent Category: Health & Fitness; Category: News & Research; Created on Friday, 25 May 2012 00:00; Hits: 4723

The Daily Mail today reports that scientists have discovered how fatty foods “trigger” type 2 diabetes. It said that the discovery may lead to a “cure” for the disease.

Obesity is a risk factor for type 2 diabetes, and this condition is becoming more common as obesity levels rise. The current study looked at whether high-fat diets might trigger the condition, by looking at the effects of a high-fat diet in mice on the insulin-producing cells of the pancreas, and on the response of cells to insulin.

The researchers found that high-fat diets in mice affected the insulin-producing cells in ways that would reduce their ability to correctly sense and respond to the presence of glucose. Tests on pancreatic tissue from people with type 2 diabetes suggested that similar changes may be occurring in humans.

This study furthers scientists’ understanding of the effects of fats on pancreatic cells, which may in turn help them to develop new treatments for the condition. However, while we wait for this, the best advice for people wanting to reduce their risk of developing type 2 diabetes is to maintain a healthy weight, do exercise and eat a healthy balanced diet. These measures can also help people with type 2 diabetes control their condition and sugar levels.

Where did the story come from?

The study was carried out by researchers from the University of California and the RIKEN Advanced Science Institute in Japan. It was funded by the US National Institutes of Health (NIH), the Eunice Kennedy Shriver National Institute of Child Health and Human Development–NIH, and the Japan Diabetes Foundation and Suntory Institute for Bioorganic Research.

The study was published in the peer-reviewed journal Nature Medicine.

The Daily Mail and BBC News cover this research appropriately. The Daily Mail emphasises the early nature of the research by quoting researchers; the BBC News gives an overview of the potential mechanisms at work.

What kind of research was this?

This animal and laboratory research investigated what events might provoke the problems with pancreatic cells that arise in type 2 diabetes.

Obesity is the main known modifiable risk factor for type 2 diabetes, a condition that is becoming more common as obesity levels rise. In type 2 diabetes, the cells in the pancreas that normally produce insulin – called beta cells – gradually stop working over time. Usually, these cells respond to increased levels of sugar in the blood by producing insulin, but this ability is lost in type 2 diabetes. Also, the cells of the body become less responsive to insulin (called insulin resistance) and don’t take up the sugar in the blood stream. These problems lead to high levels of sugar circulating around the body, which is harmful to cells and tissues.

The researchers wanted to investigate whether a high-fat diet might contribute to causing type 2 diabetes by looking at its effect on pancreatic cells.

This is an appropriate way of addressing this type of question, which is about the basic biological processes affecting the cells of the body. Results from mice or human cells in the laboratory may not be fully representative of what happens in humans, but they do give an indication of what might be happening and can lead to further research ideas.

What did the research involve?

The researchers fed mice a high-fat diet and looked at the effect of the diet on their pancreatic cells. They also investigated their findings further on mouse and human pancreatic cells in the laboratory.

In particular, they looked at what effect a high-fat diet had on the activity of certain genes and proteins in the cells that are thought to help the beta cells function. Of particular interest was a protein called GnT-4a glycosyltransferase, which in healthy pancreatic cells aids in the detection and response to glucose in the blood stream. It does this by helping to keep certain other proteins that allow the beta cells to sense glucose on the surface of these cells.

Once the researchers had a picture of what was happening in the pancreas cells exposed to fat in the laboratory and in the live mice, they also looked at pancreatic tissue from six people with type 2 diabetes to see whether their cells went through the same sort of processes.

They also genetically engineered mice to have a form of GnT-4a that was always active in the beta cells. They then looked at how these mice responded to the high-fat diet. Other mice that were genetically engineered to always have high levels of a protein involved in sensing glucose called Slc2a2 were also tested on a high-fat diet. The theory was that if dietary fat had its effects by stopping these proteins working, then these genetically engineered mice should be less susceptible to the effects of a high-fat diet.

What were the basic results?

The researchers found that when they fed mice a high-fat diet, the genes encoding the GnT-4a protein and one of the glucose sensing proteins (called Slc2a2) became less active in the mice’s pancreatic cells.

Further experiments showed that this was occurring due to effects of the high-fat diet on two other proteins called Foxa2 and Hnf1A. These proteins are involved in controlling the activity of other genes, including the genes encoding the GnT-4a protein and the glucose sensing protein Slc2a2. In order to do this they have to enter the central compartment of the cell – called the nucleus – where most of the cell’s DNA is found. In the pancreatic cells of mice on a high-fat diet, there was a reduced amount of these proteins entering the nucleus. This was found in both human and mouse pancreatic cells exposed to high levels of fats in the laboratory.

The researchers found signs that similar processes were occurring in pancreatic cells from people with type 2 diabetes.

Normal mice fed the high-fat diet showed changes similar to those seen in people with type 2 diabetes, including high levels of glucose (sugar) circulating on the bloodstream, and a reduced ability of certain tissues to respond to insulin and take up sugar. However, in mice genetically engineered to have GnT-4a work constantly in the beta cells, the high-fat diet had less of an effect on blood sugar levels and the ability of the cells to respond to insulin, even though the mice became fat.

Mice genetically engineered to have higher levels of the glucose sensing protein Slc2a2 were also less susceptible to the effects of the high-fat diet, although not to as great an extent as the mice that were genetically engineered to have GnT-4a work constantly.

How did the researchers interpret the results?

The researchers conclude that their findings suggest that a high-fat diet leads to high levels of fatty acids in the body, which stop the Foxa2 and Hnf1A proteins in insulin-producing cells from switching on production of the GnT-4a protein and glucose sensing proteins on the surface of the cell. This in turn stops the cell from responding appropriately to high levels of glucose in the blood.

They say that this suggests a biological pathway that could explain why obesity and diet can lead to type 2 diabetes.

Conclusion

This study furthers scientists’ understanding of the effects of fats on pancreatic cells. These experiments suggest that these effects may well be occurring in humans affected by type 2 diabetes. However, it is likely that further research will be needed to confirm this.

Type 2 diabetes is becoming more common as the levels of obesity rise. Better understanding of how the condition arises may help researchers to develop new treatments and preventive measures. However, these developments will take time and will need thorough testing. Whether or not it will result in the hoped-for “cure” remains to be seen.

While we wait for this research to be done, the best advice for people wanting to reduce their risk of developing type 2 diabetes is to maintain a healthy weight, do exercise and eat a healthy balanced diet. These measures can also help people with type 2 diabetes to control their condition and sugar levels.

Links to the headlines

How fatty food triggers diabetes: Scientists believe discovery paves way for Type 2 'cure'. Daily Mail, August 15 2011

Fat 'disrupts sugar sensors causing type 2 diabetes'. BBC News, August 15 2011

Links to the science

Ohtsubo K, Chen MZ, Olefsky JM et al. Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport. Nature Medicine 2011, Published online August 14