The hormones GIP and GLP-1 are important in combating obesity and type 2 diabetes. Researchers from Germany, Switzerland and the US have now conducted mouse experiments that raise hopes for a drug.
Obesity and diabetes are among the biggest health problems in the civilized worldImage: picture-alliance/G. Fuller
GIP and GLP-1 are produced in the digestive tract and play vital roles in regulating body weight and food intake. A study on their effects now published in the journal Cell Metabolism provides pointers for developing drugs to treat obesity and type 2 diabetes.
Two types of mice in the experiment
GIP acts on receptors of the central nervous system located in the brain, stimulating the release of insulin and lowering blood glucose levels. But how exactly this works has not been clear until now.
First author Qian Zhang and her team had two different types of mice at their disposal for their experiment: normal wild-type mice and specially bred mice that lacked the GIP receptors in the brain. The researchers injected both types with GIP.
Mice naturally have GIP receptors, but for the trial, scientists used specially bred mice without them Image: Imago/CTK Photo
It was found that body weight and food intake decreased in the wild-type mice, indicating that the hormone has an effect on appetite regulation. In contrast, food intake remained the same in the special laboratory mice lacking the GIP receptor. Their body weight decreased only minimally.
The researchers also looked at the mice's brain activity. "After administration of GIP, increased neuronal activity was evident in the area of the hypothalamus associated with the control of appetite ," says Christian Wolfrum of ETH Zurich.
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Approaches for drugs
As far as the treatment of type 2 diabetes goes, it is GLP-1 that plays an important role. It enhances the glucose-dependent release of insulin from the cells of the pancreas. Diabetics do not produce enough insulin themselves and have to inject it regularly.The problem is that GLP-1 is broken down again very quickly in the body and has to be constantly produced again. A solution to this problem has been available since 2005: a drug called Exenatide from AstraZeneca.
This contains an active ingredient derived from the saliva of the North American Gila monster, a venomous lizard. It acts in a similar way to GLP-1 but is not broken down as quickly by the body.
The active ingredient is therefore an "agonist." This means that it mimics the action of a hormone at a receptor and stimulates the receptor in the same way.
A similar approach using GLP-1 and GIP agonists had already been taken by researchers at Helmholtz Zentrum München together with colleagues from Indiana University. They had combined two hormones in a single molecule that acts on and stimulates both GIP and GLP-1 receptors.
This dual agonist simultaneously lowers weight and improves blood glucose levels. The researchers published their research in Science Translational Medicine in 2013.
The compound has now already entered a phase III clinical trial. It has been shown that the combination drug reduces body weight more than just one molecule does when acting at the GLP-1 receptor.
In the more recent mouse trial, it became clear, however, that the drug had no effect in mice lacking the GIP receptor in the brain. "Our work shows for the first time that the GLP-1/GIP dual agonist requires the GIP receptor in the brain to reduce body weight and food intake," said Timo Müller, last author of the new study and head of the Institute for Diabetes and Obesity (IDO) at Helmholtz Zentrum München.
His next goal is now to find further active substances to improve GIP receptor signaling because these appear to be the central mechanism for treating both conditions.
Bitter truth about sugar
Sugar is tasty, but not exactly good for you. Consumption of the sugary stuff is rising, and that’s having an impact on health. The WHO has warned of a “global epidemic.” Here are a few facts you really should know.
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Sugar makes you fat!
Sugar is converted to fat in the body about two to five times more quickly than starches. In other words, when we consume sugar, we’re feeding our fat cells. The fructose in sugar is also metabolized by the liver, which can contribute to fatty liver disease. That can promote insulin resistance and lead to Type 2 diabetes – with a lifelong impact on your health.
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Sugar affects your mood!
In small amounts, sugar promotes the release of serotonin, a hormone that boosts mood. But too much sugar can promote depression and anxiety. Sudden shifts in blood sugar levels can also lead to irritability, anxiety and mood swings.
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Sugar contributes to aging!
We already know that sugar has a variety of health effects, but it also affects the skin. That’s in part due to glycation, the process whereby sugar molecules bind to collagen fibers. As a result, the collagen fibers lose their natural elasticity. Excess sugar also damages microcirculation, which slows cell turnover. That can promote the development of wrinkles, make you look older than your age.
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Sugar is harmful to your gut!
The microflora of your gut promote digestion and protect your digestive system from harmful bacteria. Consuming too much sugar gets your gut microflora out of whack. Fungi and parasites love sugar. An excess of the Candida albicans yeast can lead to a host of annoying health symptoms. And sugar also contributes to constipation, diarrhea and gas.
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Sugar can be addictive!
In overweight people, the brain responds to sugar by releasing dopamine, in much the same way that it responds to alcohol or other addictive substances. Test it yourself: avoid all sugary foods and beverages for ten days. If you start to get headachy and irritable after a day or two, and start craving sugar, then you could be suffering from sugar withdrawal.
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Sugar makes you aggressive!
People who consume excess sugar are more likely to engage in aggressive behavior. Children with ADHD are also affected by sugar. For these children, too much sugar affects concentration and promotes hyperactivity. That’s why it’s a good idea for children to avoid eating sugar during school hours.
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Sugar weakens the immune system!
Excessive sugar consumption makes it harder for the immune system to ward off disease. After consuming sugar, the immune system’s ability to kill germs is reduced by up to 40 percent. Sugar also saps the body’s store of vitamin C, which white blood cells need to fight off viruses and bacteria. Sugar also promotes the inflammatory response, and even minor inflammation can trigger numerous diseases.
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Sugar promotes Alzheimer’s disease!
Studies have shown that excess sugar consumption increases the risk of developing Alzheimer’s disease. A 2013 study showed that insulin resistance and high blood sugar values – both of which are common in diabetes – are associated with a higher risk of neurodegenerative diseases such as Alzheimer’s.
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Sugar increases cancer risk!
Cancer cells need sugar to proliferate. An international research team headed by Lewis Cantley of Harvard Medical School is researching how sugar might contribute to the growth of malignant cells. He believes that refined sugar may be what causes cancer cells to develop into tumors. He’s still testing that hypothesis but recommends that even slender people consume as little sugar as possible.
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Sugar makes you stupid!
Excess sugar consumption may have a negative impact on memory. According to a study carried out by Berlin’s Charité University Hospital, people with high blood sugar levels have a smaller hippocampus – the part of the brain that’s key to long term memory. In the study, people with high blood sugar also performed more poorly on tests of memory than those with low blood sugar levels.
