That's it, your internal glucose (sugar) reserves are low. Fasting, sports, when supplies are lacking, our body sets in motion a process of sugar destocking... Partly regulated by the immune system. Far from being confined to defending the body against infections and diseases, certain immune cells called ILC2 are tasked by the nervous system to migrate into the pancreas, according to recent work published in the journal Science.
“ It is the first neuro-immuno-endocrine circuit supporting inter-organ communication and metabolism", rejoices Henrique Veiga-Fernandes, who led this work. In short, this is the first time that researchers have described a biological process that passes successively through the nervous system, the immune system and the production of hormones to regulate the metabolism of one organ to another.
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White blood cells signal hypoglycemia from the intestines to the pancreas
The first of these is the central nervous system, and in particular some neurons of the so-called "sympathetic" system whose endings reach the intestines. When they are informed of hypoglycemia - thanks to other glucose-sensitive neurons - the sympathetic neurons send a chemical message to the intestines. This message is received by the second actor, the immune system, and in particular cells called ICL2. ILC2s are a subset of innate lymphocytes", says Henrique Veiga-Fernandes, that is, white blood cells involved in first-line defense.
Here they reveal another role, since in response to the hypoglycemia message, they migrate towards the pancreas via the lymphatic vessels – parallel to the blood circulation. Once in the pancreas, ILC2s prompt alpha cells to produce glucagon, which then acts in the liver to induce the conversion of lipids and proteins into glucose.. »
Neuro-pancreatic and neuro-immune, two complementary circuits
Glucagon is a hormone that alpha cells in the pancreas also produce in response to direct stimulation of the sympathetic nervous system to instruct the liver to release glucose. Called the "neuropancreatic" pathway, this has been well-known for decades. The real difference between these two pathways of glucagon production is their duration of action. The newly discovered neuroimmune circuit acts in hours rather than minutes. However, it is a very sustained and vigorous stimulus that acts in synergy with the neuropancreatic axis, maximizing glucagon secretion when needed.“, explains Henrique Veiga-Fernandes.
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More sugar for longer
The alpha cells of the pancreas therefore receive the message of hypoglycemia both through their noradrenaline receptors (direct message from sympathetic neurons) or type 2 cytokines (chemical messengers from ILC2 immune cells). These distinct signals require different receptors on alpha cells, whose signals synergize to maximize glucagon secretion in a sustained and robust manner.", elaborates Henrique Veiga-Fernandes.
For his team and him, the combination of these two circuits in response to hypoglycemia could therefore allow a greater production of glucose by the liver and over a longer period than if they acted alone. We believe that the coupling of these two axes may have been essential in fight-or-flight responses that require a large amount of energy. For example, a predator chasing prey, prey fleeing a potential predator, animals fighting for a limited resource such as food or a mate, etc.. », concludes Henrique Veiga-Fernandes.
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