More than 371 million people worldwide suffer from diabetes, of whom 90% are affected by lifestyle-related diabetes mellitus type 2 (type 2 diabetes).

In new experiments, researchers from the University of Copenhagen working in collaboration with a research group at the University of Cincinnati, USA, have demonstrated that the amino acid arginine improves glucose metabolism significantly in both lean (insulin-sensitive) and obese (insulin-resistant) mice.

"In fact, the amino acid is just as effective as several well-established drugs for type 2 diabetics," says postdoc Christoffer Clemmensen. He has conducted the new experiments based at Faculty of Health and Medical Sciences, University of Copenhagen. He is currently conducting research at the Institute for Diabetes and Obesity at Helmholtz Zentrum M-nchen, the German Research Centre for Environmental Health in Munich.

To test the effect of the amino acid arginine, researchers subjected lean and obese animal models to a so-called glucose tolerance test, which measures the body's ability to remove glucose from the blood over time.

"We have demonstrated that both lean and fat laboratory mice benefit considerably from arginine supplements. In fact, we improved glucose metabolism by as much as 40% in both groups. We can also see that arginine increases the body's production of glucagon-like peptide-1 (GLP-1), an intestinal hormone which plays an important role in regulating appetite and glucose metabolism, and which is therefore used in numerous drugs for treating type 2 diabetes," says Christoffer Clemmensen, and continues:

"You cannot, of course, cure diabetes by eating unlimited quantities of arginine-rich almonds and hazelnuts. However, our findings indicate that diet-based interventions with arginine-containing foods can have a positive effect on how the body processes the food we eat."


The research findings were recently published in the American scientific journal Endocrinology under the heading Oral l-arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice.

Hormone plays key role

Researchers have known for many years that the amino acid arginine is important for the body's ability to secrete insulin. However, the latest findings show that it is an indirect process. The process is actually controlled by arginine's ability to secrete the intestinal hormone GLP-1, which subsequently affects insulin secretion.

"Mice without GLP-1 receptors are not affected to the same extent by arginine. There is no perceptible improvement in glucose metabolism or insulin secretion, confirming our hypothesis of a close biological connection between GLP-1 and arginine," says Christoffer Clemmensen, who conducted the biological experiments in the USA using a special animal model where the receptor for GLP-1 is genetically inactivated.

The new findings provide optimism for better and more targeted drugs for treating type 2 diabetes; the outlook is long-term, but promising.

"This exciting result has raised several new questions which we want to investigate. Can other amino acids do what arginine does? Which intestinal mechanisms 'measure' arginine and lead to the release of GLP-1? Finally, there is the more long-term perspective - the question of whether the findings can be transferred from mice to humans and be used to design drugs that will benefit diabetes patients," says Professor Hans Br-uner-Osborne, who is continuing work on the project in the research group at the Department of Drug Design and Pharmacology at the University of Copenhagen.
Source:

University of Copenhagen

According to a recent study from Iran, stinging nettle leaves (Urtica dioica) and walnut leaves (Juglans regia) may have potential in antidiabetic therapy. Diabetes affects over 100 million people worldwide. This disease condition causes blood glucose (sugar) levels to rise, because people with diabetes either do not make enough insulin or are unable to use insulin properly. Normally, Insulin helps glucose from blood enter muscle, brain and liver cells where it is used to generate energy. When glucose levels build up in blood, these cells become starved for energy. Over time, high blood glucose levels also damage the eyes, kidneys, nerves and heart. Carbohydrates are a major component of our daily diet. They are broken down in the gut into simple compounds called monosaccharides by the enzyme alpha-amylase before they are absorbed into the blood. Blocking the activity of alpha-amylase prevents carbohydrate digestion and has been shown to reduce blood glucose levels. In fact, ‘alpha-amylase inhibitors’ have been developed to treat diabetes in this way. While currently available alpha-amylase inhibitors do provide short-term diabetes control, they also cause serious side effects. This is why scientists are studying natural extracts from over 400 traditional medicinal plants with alpha-amylase blocking activity for their exciting potential as effective, and likely safer, antidiabetic therapies. In this study from Hormozgan University of Medical Sciences in Bandar Abbas in Iran, researchers examined the effects of leaf extracts from Urtica dioica and Juglans regia on alpha-amylase activity. U. dioica, known as the common nettle or stinging nettle, has a long history as a medicine and as a source of both food and fiber. J. regia – known as the English walnut, common walnut or California walnut – is a common food. Walnut leaves also have a long history of medicinal use. Extracts of both plants strongly blocked alpha-amylase activity. Nettle caused a 60% inhibition of the enzyme with 2 mg/ml of the extract, and walnut leaf extract required only 0.4 mg/ml for the same inhibition. This effect increased with time and dose of extract. In conclusion, the medicinal plants Urtica dioica and Juglans regia may have potential as antidiabetic therapies.   Technical Summary

    Aqueous extracts of U. dioica and J. regia showed time- and concentration- dependent inhibition of alpha-amylase. The extracts consisted of 100 g of powdered dried leaves in 100 ml of water, freeze dried to powder. The extracts demonstrated 60% inhibition of alpha amylase activity with 0.4 mg/ml of nettle leaf extract and 2.0 mg/ml of walnut leaf extract. Inhibition increased for both extracts from 40% at 5 minutes and 60% at 30 minutes. “The results showed that the type of inhibition was competitive in which enzyme-inhibitor complex could form.” This research follows the discovery that walnut leaf reduced blood sugar in diabetic rats and other supportive studies. See the full article [LINK] for all the details.

Arginine therapy may be a safe and inexpensive treatment for acute pain episodes in patients with sickle cell disease, according to results of a recent clinical study. The study was the first randomized placebo-controlled study to demonstrate benefits of arginine therapy in children with sickle cell disease hospitalized for severe pain.

Sickle cell disease is an inherited condition in which the body makes red blood cells containing abnormal hemoglobin, the protein that carries oxygen from the lungs to other cells in the body. This abnormal hemoglobin (hemoglobin S) causes red blood cells to distort into a sickle, or crescent shape that often blocks blood flow in small blood vessels, leading to pain and organ damage.

An acute deficiency of nitric oxide in sickled red blood cells contributes to the episodes of blocked vessels and pain. Since the amino acid arginine is a building block of nitric oxide, researchers hypothesized that arginine could be a beneficial treatment for pain related to sickle cell disease.

Previous research found that a single dose of arginine given to sickle cell patients with acute pain episodes resulted in a significant dose-dependent increase in plasma nitric oxide.

Building on that knowledge, the current research study was a randomized, double blind clinical trial of 38 children with sickle cell disease hospitalized for 56 episodes of pain. The research team discovered a 54 percent reduction in the use of pain medication and significantly lower pain scores at hospital discharge in those treated with arginine over those receiving placebo.


The results were published in the journal Haematologica. First author was Claudia R. Morris, MD, assistant professor of pediatrics at Emory University School of Medicine. She conducted the study while in her previous position at Children's Hospital and Research Center in Oakland, CA, with senior author Elliott P. Vichinsky, MD.

"Episodes of pain due to vaso-occlusion are the leading cause of hospital admission and emergency room visits and are associated with increased mortality, yet there is no effective therapy targeting the underlying cause," says Morris. "Treatment consists only of symptom relief with pain medicines and hydration. There is an urgent need for new therapies for acute sickle cell pain, and a greater than 50 percent reduction in use of pain medication was a remarkable finding."

The study found no problems with safety in the use of arginine therapy. Although the treatment did not result in a significantly shorter length of stay in the hospital, the researchers believe delivering the study drug as early as possible in the emergency department or clinic may have a greater impact on length of stay, since many patients received their first dose of medication more than 24 hours after presenting at the hospital.

A large, multi-center trial is warranted in order to confirm these observations and test the effects of delivering the therapy sooner, they note in the published paper.
Source:

Emory Health Sciences