Researchers from Osaka University have uncovered surprising new insights about a special form of amino acid called D-alanine. Their study, published in the journal Kidney360, reveals that D-alanine plays a key role in two important processes in the body: regulating our natural biological clock, known as the circadian rhythm, and managing glucose production through a process called gluconeogenesis.
Most people know that amino acids are the building blocks of proteins. These amino acids come in two forms: L-form and D-form. While L-amino acids are well understood and are used to build proteins in our body, D-amino acids, like D-alanine, are much less studied. Although D-alanine is present in our diet and our bodies, its role has largely been a mystery—until now.
The body’s circadian clock is like a built-in timer that follows a 24-hour cycle, influencing things like sleep, hunger, and hormone levels.
It also affects gluconeogenesis, which is the body’s way of producing glucose (sugar) from non-carbohydrate sources. This process is especially important when we haven’t eaten for a while, like during sleep or fasting, to keep our energy levels steady.
The researchers at Osaka University wanted to understand why glucose production changes based on the time of day. Their study found that D-alanine might be the missing piece of the puzzle.
It turns out that D-alanine levels in the body rise and fall in sync with the circadian clock. It is mostly found in tissues that handle glucose, and its levels fluctuate throughout the day, appearing in both the blood and urine.
To track these changes, the researchers used advanced technology to measure tiny amounts of D-alanine in the body. They discovered that these fluctuations are tied to the circadian rhythm and that the kidneys play a major role in controlling D-alanine levels by filtering it out into urine.
Interestingly, sleep was also found to affect D-alanine levels, hinting that good sleep could help maintain its natural rhythm.
To understand how D-alanine influences glucose production, the research team looked at how it affects the kidneys at the genetic level. They exposed kidney cells to D-alanine and studied which genes became more active.
Using a deep-learning computer model, they found that D-alanine boosts the activity of genes related to both gluconeogenesis and the circadian rhythm. In simpler terms, D-alanine helps the body manage its blood sugar and maintain its internal clock.
One of the key discoveries was how D-alanine interacts with a transcription factor called Cry2. Cry2 is known to regulate the circadian rhythm. When people or animals have disrupted sleep or irregular daily routines, their biological clock gets thrown off. Remarkably, the study found that adding D-alanine could help reset this clock, even under disrupted conditions.
This breakthrough suggests that D-alanine is more than just an amino acid floating around in the body—it actually helps link glucose production to our body’s natural rhythm. This connection could be important for people with conditions like diabetes, where blood sugar control is a major issue, or for those with sleep disorders linked to disrupted circadian rhythms.
The findings open up exciting possibilities for new treatments. If scientists can harness the power of D-alanine, it may lead to new ways to stabilize blood sugar levels in diabetics or help people with sleep problems get back to a healthier rhythm. More research is needed, but the discovery points to D-alanine as a potential tool for managing these conditions in the future.
For now, this study adds to our understanding of how our bodies naturally regulate energy and sleep, and it shines a light on an amino acid that has been mostly overlooked. By exploring how D-alanine interacts with the biological clock and glucose production, scientists have taken a big step toward understanding how our bodies stay balanced and healthy.
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