HCAs are a promising threat indicator of sort 2 diabetes

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A number of studies by researchers at Hong Kong Baptist University (HKBU) have shown that hyocholic acid and its derivatives (collectively known as HCAs), a component of bile acids that make fat digestion easier, are a promising risk indicator for type 2 are diabetes. The potent effectiveness of HCAs in regulating blood sugar levels and protecting against diabetes was also discovered. The results open a window for the development of HCA-based predictive markers as well as antidiabetic drugs.

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

A 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 now known as diabetes, Professor Jia Wei, Chair Professor of the School of Chinese Medicine at HKBU, directed Research teams to conduct a series of studies on the role of HCAs in glucose homeostasis and diabetes prevention.

Diabetes is characterized by high blood sugar levels. Through a series of tests on 55 people, 32 mice and 12 pigs, Professor Jia’s team confirmed that fasting blood sugar levels in pigs are significantly lower than in humans and mice. Since HCAs account for almost 80% of the 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 sugar levels has been observed.

The result shows the potential role of HCAs in maintaining stable glucose levels. This could explain why, unlike humans, pigs rarely have diabetes despite their low physical activity and consumption of a high-calorie diet.

HCAs correlate with diabetes and metabolic health

To analyze the correlation between HCA levels and the incidence of diabetes in humans, data were 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 in the 2013 Shanghai Obesity Study. Participants were divided into three groups: healthy lean, healthy obese, and obese with type 2 diabetes. It was found that serum HCA levels were significantly lower in healthy obese people and obese people with type 2 diabetes groups.

Another study examined the serum bile acids of 132 participants in the Shanghai Diabetes Study. They were all healthy (at baseline) when they entered the study between 1998 and 2001. Ten years later, 86 of them had become metabolically unhealthy while 46 remained healthy. The analysis found that compared to those who remained healthy ten years later, those who became metabolically unhealthy had significantly lower baseline serum HCAs, indicating that HCA levels are a strong predictor of metabolic syndromes such as diabetes are.

HCAs regulate blood sugar levels in animal models

In a series of laboratory experiments, the researchers examined the mechanisms that support the key role HCAs play in regulating blood sugar levels. In an animal model experiment, the researchers suppressed the synthesis of HCAs in the livers of a group of pigs by about 30% and found that their blood sugar levels increased by 30% compared to the control group. The pigs were then given HCAs and their blood sugar levels decreased.

Another experiment conducted by the researchers focused on the effects of HCAs on glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone produced by L cells, a type of enteroendocrine cell that improves insulin secretion and lowers blood sugar. Various types of bile acids, including HCAs, were applied to L cells in varying concentrations in a laboratory setting. The results showed that HCAs at a high concentration of 50 micromolar compared to other types of bile acids were most effective at stimulating GLP-1 secretion. The results also showed that HCAs regulate blood sugar levels by stimulating the secretion of GLP-1 and thus insulin production.

Potential for Predicting and Treating Diabetes

The results of our studies provide clues as to how HCAs help regulate blood sugar levels and the mechanism by which this is achieved at the cellular level. HCAs show great promise and could become a drug for the prediction and treatment of type 2 diabetes. “

Professor Jia Wei, Chair Professor of the School of Chinese Medicine, HKBU

“Since gut microbiota can regulate the metabolism of HCAs, targeting the gut instead of the pancreas could be a prospective new strategy for treating diabetes. We will continue to investigate how to increase secretion levels of HCAs in diabetics by regulating gut bacteria.” he added.

Source:

Hong Kong Baptist University

Journal reference:

X. Zheng et al. (2021) Hyocholic acid species as novel biomarkers for metabolic disorders. Nature communication. doi.org/10.1038/s41467-021-21744-w.