Hong Kong Baptist University-led research reveals hyocholic acids are promising agents for diabetes prediction and treatment

HONG KONG SAR – Media
OutReach – 1 April 2021 – A series of studies
led by researchers from Hong Kong Baptist University (HKBU)
have revealed that hyocholic acid and
its derivatives (collectively known as HCAs), a component of bile
acids that facilitate fat
digestion, are a promising risk indicator of type 2 diabetes. The strong
efficacy of HCAs in regulating blood glucose levels and protecting against diabetes has also been uncovered.
The findings open a window for the development of HCA-based predictive markers
as well as anti-diabetic drugs.

Professor Jia Wei, Chair Professor of the School of Chinese Medicine at HKBU, has revealed that hyocholic acid and its derivatives are a promising risk indicator of type 2 diabetes.

 

The
research results have been
published in the international scientific journals Cell Metabolism and Nature Communications.

High concentration
of HCAs protects pigs from diabetes

 

Inspired
by the traditional Chinese medical book Compendium
of Materia Medica, which recorded the use of pig bile to treat excessive
thirst, a condition known today as diabetes, Professor Jia Wei, Chair Professor
of the School of Chinese Medicine at HKBU, led research teams to conduct a
series of studies on the role of HCAs in glucose homeostasis and diabetes
prevention.

 

Diabetes
is characterised by high blood glucose levels. Through a series of tests
conducted on 55 humans, 32 mice and 12 pigs, Professor Jia’s team confirmed
that fasting blood glucose levels in pigs are significantly lower than that of
humans and mice. As HCAs constitute nearly 80% of bile acids in pigs, while the
proportions in humans and mice are only about 2% and 3% respectively, a negative correlation between HCAs and
blood glucose levels was observed.

 

The
result indicates the potential role of HCAs
in the maintenance of stable glucose levels. This may explain why pigs,
unlike humans, seldom suffer from diabetes despite their low physical activity
levels and consumption of a calorie-rich diet.

 

HCAs correlate
with diabetes
and metabolic health

 

To
analyse the correlation between the levels of HCAs and the occurrence of
diabetes in humans, data was collected from two large-scale cohort studies, namely
the Shanghai Obesity Study and the Shanghai Diabetes Study. The researchers examined
the serum bile acid profiles of 1,107 participants of the Shanghai Obesity
Study, which was published in 2013. The participants were divided into three
groups: healthy lean, healthy obese and obese with type 2 diabetes. It was
discovered that the levels of serum HCAs
were significantly lower in the healthy obese and obese with type 2 diabetes
groups.

 

In
another study, the serum bile acids of 132
participants of the Shanghai Diabetes Study were investigated. They were all
healthy (at baseline) when they were enrolled in the study between 1998 and
2001. Ten years later, 86 of them had become metabolically unhealthy, while 46
remained healthy. Analysis showed that, compared with those who remained healthy
ten years later, those who had become
metabolically unhealthy had significantly lower baseline levels of serum HCAs, illustrating
that levels of HCAs are a strong predictor of metabolic syndromes such as
diabetes.

 

HCAs regulate
blood glucose levels in animal models

 

Through
a series of laboratory experiments, the researchers looked further into the
mechanisms that underpin the key role that HCAs play in regulating blood
glucose levels. In an animal model experiment, the researchers suppressed the synthesis
of HCAs in the livers of a group of pigs by around 30%, and they found that their
blood glucose levels increased by 30% when compared with the control group. HCAs were then given to the pigs, after
which their blood glucose levels eased off.

 

Another
experiment conducted by the researchers focused on the effect of HCAs on
glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone produced by L-cells, a type
of enteroendocrine cell that enhances insulin secretion and decreases blood
glucose. In a laboratory setting, different kinds of bile acids, including
HCAs, were applied to L-cells, at varying levels of concentration. Results
showed that at a high concentration of 50 micromolar, HCAs were the most
effective at stimulating GLP-1 secretion when compared with other types of
bile acids. The findings also revealed that HCAs regulate blood glucose
levels by stimulating the secretion of GLP-1 and thus insulin production.

 

Potential for
diabetes prediction and treatment

 

“The
results of our studies provide evidence of how HCAs help to regulate blood
glucose levels, and they have revealed the mechanism of how it is achieved at a
cellular level. HCAs demonstrate promising potential, and they could be developed
into an agent for the prediction and treatment of type 2 diabetes,” said
Professor Jia.

 

“As gut microbiota can regulate the
metabolism of HCAs, targeting the intestines instead of the pancreas could be a
prospective novel strategy for treating diabetes. We will further investigate how
to increase the secretion levels of HCAs in diabetic patients by regulating the
intestinal bacteria,” he added.

 

Researchers from the Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Peking University, the Affiliated Drum Tower Hospital of Nanjing University Medical School, China Academy of
Chinese Medical Sciences, China Agricultural University, Sichuan University and the
University of Hawaii were also involved in the studies.