To prevent high blood sugar, start with “relaxing the heart”


Screenshot of the paper

14 November marks the sixteenth United Nations Diabetes Day. According to the World Health Organization, deaths from diabetes increased by 3% between 2000 and 2019. In recent years, the prevalence of diabetes in China has remained high, with the prevalence of diabetes in adults in China being 11.6% in 2010 and 12.4% in 2018. It should be noted that the age of onset of diabetes is gradually earlier, and the reason for this may be related to the pressure, anxiety or mood swings faced by young people. So, what is the pathological mechanism behind mood swings and mental stress leading to elevated blood sugar?

On November 8, the latest research results published by Wang Liping’s team from the Institute of Brain Cognition and Brain Diseases/Shenzhen-Hong Kong Innovation Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (hereinafter referred to as “Shenzhen Advanced Institute”) answered this question. Dr. Jia Xianglian is the first author of the research results, Professor Wang Liping is the corresponding author of the paper, and Shenzhen Advanced Institute is the first unit of the paper.

In fact, blood sugar scheduling, as an instinctive and life-and-death strategy for the body to cope with physical or psychological stress—that is, when in danger, the body can mobilize energy reserves to “escape or fight”—has been conservatively passed down from the beginning of biological evolution, indicating that in animals, the brain processes psychological stress and blood sugar metabolism as a “coordinated sharing” mechanism.

Wang Liping’s team has been committed to the study of the neural mechanism of instinctive behavior, using animal behavior experiments combined with high-precision neural circuit tracing and regulation technology to explain how the body maintains the underlying control logic of homeostasis through behavioral output and physiological regulation. In this study, the research team discovered through a series of animal experiments that neural circuits activated by stress stress in the brain can be “parallelized” anxiety-like behavior and blood sugar regulation by projecting to different downstream brain regions, which further deepens the understanding of the pathological mechanism of negative emotions and blood glucose metabolism disorders, and also provides new potential targets for future intervention in comorbidities of the mental and metabolic systems.

Physical restraint is an uncomfortable stimulus for mice, and short-term restraint can cause negative emotions in mice, but it will not cause organic damage. The researchers found that just 5 minutes of physical restraint caused anxiety-like behavior in mice, accompanied by an acute rise in blood sugar and glucagon, indicating that the brain can respond quickly to external stimuli while producing emotional responses, and then regulate blood sugar changes through this “loop parallel processing” mechanism.

In addition, the team comprehensively used cutting-edge neuroscience technologies such as optogenetic regulation, electrophysiological recording, and viral tracing, and also found that the neural circuits of glutamate decarboxylase (Gad2) neurons of the final stria bed nucleus (BNST) projected to the arcuate nucleus (ARC) of the hypothalamus are significantly activated in this process.

By further utilizing the “tertiary neural circuit regulation” strategy combined with chemogenetics, the researchers found that ARC can project to the mesosuture cryptonucleus (ROb) and the solitary bundle nucleus (NTS) located in the medulla oblongata (the life center of the body), respectively, and that the cells that ARC projects to the two downstream nuclei are not exactly the same group. At the same time, further experiments showed that when pharmacogenetic methods were used to inhibit the activity of ROb, even if the BNST-ARC circuit was activated to produce anxiety-like behavior, there would be no increase in blood sugar. In contrast, when pharmacogenetics inhibited NTS activity, activation of the BNST-ARC circuit, although it did not cause anxiety-like behavior, still showed a rise in blood sugar. This shows that when stress comes, the BNST-ARC-ROb loop is essential for the body to quickly call blood sugar, and BNST-ARC-NTS is a key nucleus that affects whether the body has anxious behavior.


Two parallel loops mediate stress-induced anxiety-like behavior and blood sugar rise, respectively Courtesy of the research team

“We were surprised to find that the brain harnesses limited neuronal resources and coordinates behavior and homeostasis through precise classification and network connectivity to achieve a rapid response to external stressors.” As the body’s ‘commander’, while feeling the challenges of the external environment, specific neural circuits can also rapidly regulate glucose metabolism states, and the physical structure and logic encoded by the brain deserve more in-depth exploration. First author Dr. Jia Xianglian said.

“This is not the first time that we have found the existence of this ‘efficient’ strategy of the brain in our work, this discovery shows that the brain further coordinates the emotional behavior of animals and the maintenance of homeostasis in the body through a more detailed and precise network structure on the basis of ‘sharing’; I believe that this conservative and universal coding logic will provide new ideas for people’s understanding of the body’s self-healing intelligence.” Our current research also suggests that the body is an inseparable whole, mental changes often interact with peripheral physiological function changes, the previous reductionist perspective of ‘headache and foot pain’, to a large extent need to combine ‘holistic view and systems theory’, this logic is expected to provide a unique research perspective for a comprehensive understanding of the brain’s function in the body’s homeostatic regulation. Corresponding author researcher Wang Liping said. (Source: China Science News, Diao Wenhui, Sun Lujia)

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