Researchers have discovered a plant extract that targets the glucose-regulating regions of the brain that are inflamed in type 2 diabetics, improving blood glucose levels. The findings open the door to a novel, natural treatment for the disease.
Type 2 diabetes (T2D) affects how the body uses glucose (sugar) for energy. It’s caused by a combination of ineffective insulin and not enough insulin. T2D is often preventable, especially when risk factors such as weight, exercise and diet are addressed.
Early diagnosis of the disease is important to prevent or delay its progression. Prediabetes is when blood glucose is high but not high enough to be considered T2D and indicates impaired glucose tolerance. It often presents with mild symptoms that can go unnoticed, but prediabetes is likely to develop into T2D without intervention.
Given that T2D is the more prevalent form of diabetes, representing around 98% of global diabetes diagnoses, it’s important that the disease be treated early and effectively. Now researchers at the University of Otago, New Zealand, have discovered a plant extract that acts on the glucose-regulating regions of the brain to improve blood glucose regulation in type 2 diabetics.
It's widely accepted that pathways in the brain are responsible for glucose regulation. In non-diabetics, circulating insulin – the hormone that moves glucose from the bloodstream into the body’s cells to make energy – reaches the hypothalamus, a small area in the center of the brain. This sets off a chain reaction that mediates the effects of insulin. Studies have shown that inflammation of the hypothalamus plays a key role in leading to insulin resistance, a hallmark of T2D.
From prior research on mice, the researchers knew that butein, a plant-derived compound, produced marked glucose-lowering and insulin-sensitizing effects in obese and glucose-intolerant mice by reducing inflammation in the hypothalamus. They decided to explore whether an extract taken from the petals of the dahlia flower (Dahlia pinnata), a known source of butein, could be exploited as a novel treatment for prediabetes and T2D in humans.
After creating an extract from the dahlia flower petals, the researchers tested it in different doses on mice fed a high-fat diet (HFD) to see if it affected glucose tolerance. Doses were administered orally one hour before a glucose tolerance test was performed. They found that a 10 mg/kg body weight dosage produced improved glucose tolerance and insulin sensitivity in the HFD-fed mice. The extract did not affect blood glucose levels in healthy control mice fed a low-fat diet.
To test whether the effect could be sustained, researchers treated the HFD-fed mice with dahlia extract daily for five weeks. The HFD-fed mice that received long-term treatment with the extract showed improved glucose tolerance compared with mice that didn’t receive the extract. Examining the livers of the mice, the researchers found no signs of toxicity.
The researchers then looked at what was causing the effects they observed. They noted that, besides butein, the dahlia extract contained two other compounds, isoliquiritigenin and sulfuretin. While isoliquiritigenin and sulfuretin alone, or a combination of the two, were relatively ineffective in improving glucose tolerance, they found that, in combination, the three compounds produced a significant improvement.
Examining the brains of the mice, the researchers found that the dahlia extract appeared to reduce inflammation in the hypothalamus, suggesting that the glucose-lowering properties of the extract were mediated by its anti-inflammatory action. Having demonstrated the effect of dahlia extract in mice, the researchers tested it in a "first-in-human" trial.
Conducting a randomized controlled trial involving 13 participants with prediabetes or T2D, they found that the dahlia extract improved glucose tolerance in participants with both conditions. In those who fit the World Health Organization (WHO) criteria for a diagnosis of T2D, a dose of 60 mg/m2 produced a more pronounced glucose-lowering effect, suggesting that the extract had an increased effect on those who’d already progressed from prediabetes to T2D. Results of pre-treatment blood tests to analyze liver function, renal function, and overall health didn’t differ after treatment with the extract.
“Impaired blood sugar regulation is a debilitating condition affecting millions of people are the world,” said Alexander Tups, corresponding author of the study. “I hope and I really believe that the outcome of our intensive research will benefit people suffering from this condition.”
The researchers are working with external stakeholders to bring a natural dahlia extract supplement to the market.
The study was published in the journal Life Metabolism.
Source: University of Otago
