Beta cells, diet and new drugs
After studying pharmacology at Linköping University, Albert Salehi wanted to go on to study medicine. By chance he came into contact with Professor Ingemar Lundqvist, who was doing research on beta cells and diabetes at the Department of Pharmacology in Lund, and his planned medical studies thus came to be replaced by diabetes research at Lund University.
“I wanted to test whether it was possible to find a real cure, or in some way prevent the development of diabetes, both in children and adults”, says Albert Salehi, who today leads a research group at Lund University Diabetes Centre in Malmö.
He is convinced that it is only a matter of time before there will be new medicines for diabetes.
“Detailed knowledge of the mechanisms of how the insulin cells function has improved during last decades. When I started, the research had not got very far. I wanted to change things and see whether it was possible to develop drugs other than metformin and sulphonylurea, which had essentially been the only drugs for treatment of type 2 diabetes since their introduction in the 1970s and the 1950s.”
Insulin is an essential hormone that is released when we eat to keep our blood sugar at a very narrow fluctuating level. Insulin is produced by pancreatic beta cells in response to a wide range of metabolic, hormonal or neuronal factors where each of which alone or in combination produce signals to maintain a normal b-from receptors on the surface of the cell.
Too low blood sugar can lead to a coma and too high blood sugar can lead to damage to blood vessels and other organs.
In healthy individuals, the body manages to regulate its blood sugar levels, but in people with type 1 diabetes, the correct amount of insulin must be supplied at before each meal. People with type 2 diabetes can influence the regulation of blood sugar using diet and exercise, but sometimes when a satisfactory result is not achieved, they have to supplement this with drugs like metformin and sulphonylurea.
When you take the medicine always a certain reduction of the effect may show up, but if you switch between drugs with different mechanisms of action, the negative “effect” of the drug on the cell can be avoided.
The same principle can also apply to beta cell. To maintain a functional beta cell for a long time in the treatment of type 2 diabetes, we need to have a wide range of newer antidiabetic drugs.
“It’s the same for beta cells that become worn out. Once they are exhausted, you have to take insulin. In order to avoid patients ending up in that situation, we do all we can to help them to keep their own beta cells for as long as possible. It is therefore important to develop new drugs that can entirely or temporarily replace the old ones.”
What is it in food that stresses the beta cells to such an extent that they eventually die is another aspect in my research!
In order to understand this, we first have to understand what happens to the food we eat and how that affects the beta cells.
Food is made up of fat, protein and carbohydrates; and in the body all carbohydrates are converted to glucose, i.e. sugar.
“Our results show that large amounts of sugar are not good for the beta cells. White rice, rapidly boiled pasta and white bread are all absorbed by the body in the form of sugar. Cakes and sweets are more quickly converted to sugar”, says Albert Salehi.
In order to convert the sugar to energy and regulate blood sugar levels, the beta cells release insulin. If we don’t use up the energy, it is converted into fat and stored in various organs.
According to Albert Salehi, we should therefore primarily be careful of fast acting carbohydrates, as overconsumption can lead to obesity.
“For many years, people in Sweden, and the media, have been attacking fat, but it is actually sugar that is ‘dangerous’, because it leads to obesity with overconsumption, which in turn can lead to cardiovascular disease and type 2 diabetes.”
Fast-acting carbohydrates in the form of sugar, white bread, white rice and rapidly boiled pasta prompt the body to release large amounts of insulin. Apart from reducing blood sugar levels, this also creates a feeling of hunger.
“Some foods, such as fruit yogurts, contain large amounts of carbohydrate”, says Albert Salehi, adding that children in particular are easily enticed to eat too much of these because the food is sweeter and tastier with added sugar.
In his research, he has also shown that whey, a by-product in cheese production, causes a less steep increase in insulin release and a longer-lasting feeling of satiety.
“This could lead to new foods that are better adapted to diabetics, and those who need to lose weight or who are watching their weight”, he says.
He thinks that Sweden’s National Food Agency should alter its dietary guidelines, reducing the recommended amount of carbohydrate and increasing the protein.
This sounds like the Swedish LCHF diet (Low Carb High Fat), which is a particularly controversial hot potato in the research community.
“I have nothing against LCHF”, says Albert Salehi, who has seen in his research that carbohydrates not only cause changes to the beta cells, but also to the liver and muscles.
He therefore advises healthy individuals to reduce their overconsumption of carbohydrates and not to snack constantly.
“The best thing is to eat in moderation and not to always be munching on something.”
However, if you have diabetes, you should be careful of foods that contain a lot of fast acting carbohydrates, since diabetic patients do not release an appropriate amount of insulin to counteract the rising blood sugar, which leads to higher levels of HbA1C (the long-term average blood sugar level), that in turn can lead to complications.
“Healthy individuals have a reasonable HbA1C level even if they eat a lot of carbohydrates.”
Insulin production, or insulin release, can also be amplified partly in response to various signals initiated by certain cell surface proteins so called ‘G protein-coupled receptors’ (GPCR) activation. There are several hundred G protein-coupled receptors, and we have identified a wide numbers of these GPCRs in the islets and we believed that they are involved in the regulation of insulin production and secretion. These GPCRs are thus an attractive target for the development of new drugs in the treatment of obesity and type 2 diabetes. Hence, an increased secretion of insulin (seen in obese people) or a reduced insulin secretion (seen in type 2 diabetic subjects) can be pharmacologically modified by activation or inhibition of certain GPCRs.
According to Albert Salehi, the receptors are easy to activate or to block, which could lead to future personalized medications since there might be gender differences as well as differences in obese diabetic and thin diabetic subjects.
The problem is that drug development is a long and costly process.
“The pharmaceuticals industry in Sweden is not focused on diabetes, and for the industry to be interested, they must be sure they are going to make a profit.
“In order to develop a drug, there must be funding and people who can do the work.”
In the meantime, Albert Salehi is testing substances in existing drugs to see what effect they have on the G protein-coupled receptors.
The different types of diabetes are complex conditions that can have multiple causes.
Reduced function of insulin cells can also have a number of causes. A few years ago, Albert Salehi discovered that the female sex hormone oestrogen protects against type 2 diabetes.
“Before the age of 50, there are fewer diabetic women than men, but after the menopause they catch up. We were able to show that oestrogen has a protective effect on the insulin-producing cells, and other researchers have confirmed our findings later.”
Albert Salehi says that there are results that have not yet been published showing that certain vitamins also activate these receptors and help to protect the beta cells.
Even if many researchers are still occupied with studying beta cells, Albert Salehi´s work has helped to improve knowledge of them.
It remains to be seen what will come first – the new drugs or new dietary guidelines.