Internal body signals important for diabetes research

A joint research project between Sweden and the USA has uncovered a so far unknown signal network involving the cells in the pancreas. This discovery has the potential to significantly revolutionise the treatment of diabetes. Diabetes has an enormous impact on the lives of families worldwide. Its impact can be measured both in economic terms and in terms of human lives. According to the World Health Organization (WHO), diabetes is expected to have caused 3.8 million deaths worldwide in 2007. In Europe alone, around 7.8% of the population suffers from diabetes. Over 48 million adults aged 20 to 79 years in Europe live with diabetes with rates generally at a higher level in the countries of central and eastern Europe.

A new discovery by the scientists at Sweden's Karolinska Institute and Miami University in the US may lead to the development of novel treatments that will combat diabetes. The team has discovered that the cells in the pancreas cooperate - and communicate - in a way that up until now had not been recognised.

Scientists have known for a long time that glucose is regulated with the help of hormones in the pancreas. In more scientific terms, what this means is that the pancreatic beta cells produce insulin, which reduces sugar levels, and that alpha cells produce glucagon, which boosts them. This glucose balance must be kept within a very narrow interval, and people need the correct balance of both insulin and glucagon to remain in good health. The aim of the project was to find out how the healthy body regulates glucose concentrations in the blood.

Per-Olof Berggren is a professor of experimental endocrinology at the Karolinska Institute and is also the leader of this research study. "A person with low blood sugar levels feels poorly and faint; a person with excessively high blood sugar levels gets diabetes," he comments.

Professor Berggren's team focused their efforts on glucagon secretion, which has not been as widely researched as insulin secretion. What they discovered was that alpha cells also secreted glutamate. This secretion facilitates glucagon release and makes it more efficient.

The scientists began by working on the hypothesis that when glucose levels are raised in a healthy person, the beta cells become active and start to release insulin, which reduces sugar concentrations in the blood, upon which the alpha cells then start to secrete glucagon and glutamate. In this context, glutamate acts as a positive signal that tells the alpha cells that it is time to accelerate the production of glucagon to prevent glucose levels from falling too low.

"It's this signal pathway that is our discovery," explains Professor Berggren. "This interaction between beta cells and alpha cells is crucial for normal blood sugar regulation."

The discovery also means that when the beta cells fail to produce insulin properly, as is the case in diabetes, the alpha cells' signal path is also blocked, which upsets the glucose balance even more. The team hope that their discovery of the signal pathway will eventually give new impetus to clinical diabetes research.

"Maybe we'll be able to achieve better blood sugar regulation in diabetes patients if we target more the glucagon/glutamate rather than just the insulin," says Professor Berggren.

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