Amino acid with promising anti-diabetic effects

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 München, 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 Bräuner-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.