Biochemical controls: very many in the gut (Introduction)
Using organoids to study specific controlling cells:
https://www.science.org/doi/10.1126/science.adl1460?utm_source=sfmc&utm_medium=emai...
"Enteroendocrine cells are a collection of cell types found throughout the gastrointestinal tract that secrete various hormones involved in digestion and metabolism. These cells are relatively rare, and they vary in their locations and the types of hormones they secrete, making it difficult to fully characterize their subtypes and biological functions. To address this difficulty, Beumer et al. developed a method of culturing organoids composed of human gastric cells. The authors then studied organoids derived from the stomach, small intestine, and colon cells of human patients with or without targeted mutations inactivating specific receptors to delineate the functions of various metabolite sensors and to identify potential pharmacological targets.
***
"Enteroendocrine cells (EECs) are gut epithelial cells that respond to intestinal contents by secreting hormones, including the incretins glucagon-like peptide 1 (GLP-1) and gastric inhibitory protein (GIP), which regulate multiple physiological processes. Hormone release is controlled through metabolite-sensing proteins. Low expression, interspecies differences, and the existence of multiple EEC subtypes have posed challenges to the study of these sensors. We describe differentiation of stomach EECs to complement existing intestinal organoid protocols. CD200 emerged as a pan-EEC surface marker, allowing deep transcriptomic profiling from primary human tissue along the stomach-intestinal tract. We generated loss-of-function mutations in 22 receptors and subjected organoids to ligand-induced secretion experiments. We delineate the role of individual human EEC sensors in the secretion of hormones, including GLP-1. These represent potential pharmacological targets to influence appetite, bowel movement, insulin sensitivity, and mucosal immunity.
"Enteroendocrine cells (EECs) are gastrointestinal (GI) epithelial cells that constitute part of the gut-brain axis. They regulate physiological responses related to metabolism such as appetite, insulin release, and bowel movement, as well mucosal immunity (1). EECs are relatively rare (~1% of the epithelium) and can be subdivided into five major subtypes, each producing a different set of peptide hormones and/or neurotransmitters (2). Each subtype has a distinct distribution along the GI tract. The major EEC subtype, the enterochromaffin cell (EC), produces ~90% of the body’s serotonin (5-HT) and regulates gut motility and inflammation. The other EECs are coded with letters: L cells produce glucagon-like peptide 1 (GLP-1), neurotensin (NTS), peptide YY (PYY), and cholecystokinin (CCK); MX cells produce ghrelin (GHRL) and motilin (MLN); D cells produce somatostatin (SST); K cells produce gastric inhibitory protein (GIP); and G cells produce gastrin (GAST) (3). K, MX, and G cells are most abundant in the proximal small intestine (SI), whereas L cells are enriched in the distal SI and colon. The stomach corpus contains an EEC subset called enterochromaffin-like (ECL) cells. In addition to producing some 5-HT, ECL cells produce histamine to regulate acid secretion by nearby parietal cells (4). Important differences exist between mouse and human EECs. For instance, human MX cells express motilin only in the SI but not in the stomach (where these are called X cells), whereas the pertinent gene is a pseudogene in rodents.
"EECs are electrically excitable and control hormone secretion through elevation of intracellular calcium (5). Calcium levels are controlled through G protein–coupled receptors (GPCRs), as well as nutrient status, regulating the activity of adenosine triphosphate (ATP)–sensitive potassium channels. Their products can signal to local neurons, potentially through diffusion or through synaptic interactions (called neuropods) with nearby neurons (6), immune cells and to other epithelial cells.
Here are the scientist's thoughts:
https://mail.google.com/mail/u/0/#inbox/FMfcgzQXJswcxrBPRJQjRJnBBshhKQzr
"...everyone knows that the intestine is where nutrient uptake happens. But what I think is much less known is that it’s also the largest endocrine organ. The intestine has the most hormone-producing cells of any tissue—the enteroendocrine cells. Even though they’re very rare within it—they’re less than 1% of the epithelium, or the layer that lines the intestine—because the intestine is so large, it’s still a lot of cells. And these cells act as first responders. Whenever you eat, they are sitting there and watching what comes into the lumen of the gut, or the inside of that intestinal tube. They chemically “see” that food, and they prepare the body for what’s coming by secreting hormones. These cells can even respond to the stretching of the tissue." (my bold)
"They do a lot—they can tell your brain to eat more or less. They regulate gut motility and blood glucose levels. And because of these physiologically important roles, they’re of course very interesting targets for therapies as well."
Comment: This is high powered research which I have introduced here with direct quotes from a science journal. It is not meant to educate at that level, but to show that extremely complex design exists to run our bodies.
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2024-10-02, 23:06
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David Turell,
2024-10-08, 20:00
- Biochemical controls: -
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2024-10-09, 18:33
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2024-10-12, 20:09
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David Turell,
2024-10-19, 18:08
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- Biochemical controls: very many in the gut - David Turell, 2024-10-30, 17:05
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David Turell,
2024-10-27, 18:12
- Biochemical controls: checking on harmful invaders -
David Turell,
2024-10-22, 20:16
- Biochemical controls: consuming dead cell garbage -
David Turell,
2024-10-19, 18:08
- Biochemical controls: how sperm and egg say hello -
David Turell,
2024-10-18, 18:21
- Biochemical controls: predicting seasonal change -
David Turell,
2024-10-12, 20:09
- Biochemical controls: -
David Turell,
2024-10-09, 18:33
- Biochemical controls: chaperones control proteins -
David Turell,
2024-10-08, 20:00
- Biochemical controls: how endosymbiosis starts -
David Turell,
2024-10-02, 23:06
- Biochemical controls: an RNA controls cell death -
David Turell,
2024-10-02, 19:13
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David Turell,
2024-09-27, 19:37
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David Turell,
2024-09-25, 20:26
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David Turell,
2024-09-21, 18:07
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David Turell,
2024-09-18, 20:16
- Biochemical controls: cells on the edge of chaos -
David Turell,
2024-09-18, 18:42
- Biochemical controls: intracellular communication -
David Turell,
2024-09-16, 19:32
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David Turell,
2024-09-12, 18:26
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David Turell,
2024-09-09, 20:16
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David Turell,
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David Turell,
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David Turell,
2024-09-06, 19:13
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David Turell,
2024-09-01, 16:28
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David Turell,
2024-08-27, 19:28
- Biochemical controls: providing T cell memories -
David Turell,
2024-08-25, 19:27
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David Turell,
2024-08-22, 18:33
- Biochemical controls: mitochondrial self-repair -
David Turell,
2024-08-22, 00:10
- Biochemical controls: plant immunity against viruses -
David Turell,
2024-08-13, 21:36
- Biochemical controls: over natural killer cells -
David Turell,
2024-08-12, 18:31
- Biochemical controls: symbiotic controls -
David Turell,
2024-08-09, 20:03
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David Turell,
2024-08-09, 19:37
- Biochemical controls: plant controls genetic or not -
David Turell,
2024-08-02, 18:33
- Biochemical controls: long-lived proteins in oocytes -
David Turell,
2024-07-21, 16:53
- Biochemical controls: rythymic gene expression in symbiosis -
David Turell,
2024-07-20, 21:11
- Biochemical controls: a protein guides cell division -
David Turell,
2024-07-20, 20:44
- Biochemical controls: why apoptosis? -
David Turell,
2024-03-06, 18:16
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David Turell,
2024-03-04, 18:42
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David Turell,
2024-02-28, 18:57
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David Turell,
2024-02-08, 20:34
- Biochemical controls: mitochondrial energy output -
David Turell,
2024-01-21, 20:02
- Biochemical controls: intercellular communication -
David Turell,
2024-01-19, 19:10
- Biochemical controls: cellular molecular decision making -
David Turell,
2024-01-18, 18:59
- Biochemical controls: mitochondrial vast activities -
David Turell,
2024-01-08, 19:04
- Biochemical controls: how age is controlled -
David Turell,
2024-01-08, 17:35
- Biochemical controls: cell adhesion controls -
David Turell,
2024-01-08, 17:17
- Biochemical controls: cellular health controls -
David Turell,
2024-01-06, 20:05
- Biochemical controls: intracellular reactions -
David Turell,
2023-12-21, 20:16
- Biochemical controls: enormous number of molecular reactions -
David Turell,
2023-12-11, 19:55
- Biochemical controls: enzymes control insulin level -
David Turell,
2023-12-06, 14:59
- Biochemical controls: reading DNA -
David Turell,
2023-11-24, 22:19
- Biochemical controls: condensate formation in cells -
David Turell,
2023-11-13, 22:00
- Biochemical controls: how T cells fight cancer -
David Turell,
2023-11-11, 16:55
- Biochemical controls: how mitochondria protect themselves -
David Turell,
2023-11-10, 19:09
- Biophysical controls: motors looping DNA -
David Turell,
2023-11-10, 15:54
- Biophysical controls -
David Turell,
2023-10-25, 21:36
- Biochemical controls: handling stress -
David Turell,
2023-10-16, 18:59
- Biochemical controls: making operational synapses -
David Turell,
2023-10-12, 21:35
- Biochemical controls: new cell division discovery -
dhw,
2023-10-08, 11:47
- Biochemical controls: new cell division discovery -
GateKeeper,
2023-10-08, 00:24
- Biochemical controls: garbage disposal -
David Turell,
2023-08-26, 20:33
- Biochemical controls: treadmilling for cell division -
David Turell,
2023-08-25, 20:54
- Biochemical controls: cell control of mRNA -
David Turell,
2023-08-25, 20:42
- Biochemical controls: molecular language -
David Turell,
2023-08-17, 17:19
- Biochemical controls: nucleolus formation -
David Turell,
2023-08-15, 17:10
- Biochemical controls: cell division atomic level -
David Turell,
2023-08-14, 17:40
- Biochemical controls: plant controls for gravity -
David Turell,
2023-08-13, 23:08
- Biochemical controls: FUBI's role -
David Turell,
2023-08-12, 00:19
- Biochemical controls: molecular movements -
David Turell,
2023-08-10, 18:52
- Biochemical controls: parasites control hosts - David Turell, 2024-05-02, 21:00
- Biochemical controls: making insulin -
David Turell,
2023-07-25, 18:02
- Biochemical controls: parasites control hosts -
David Turell,
2023-07-20, 18:05
- Biochemical controls: expanding bacterial walls -
David Turell,
2023-07-20, 17:43
- Biochemical controls: oxygen without photosynthesis -
David Turell,
2023-07-17, 16:52
- Biochemical controls: plant root growth factors -
David Turell,
2023-07-08, 18:23
- Biochemical controls: intracellular quantum actions - David Turell, 2023-09-09, 21:25
- Biochemical controls: photosynthesis from one photon -
David Turell,
2023-07-05, 16:10
- Biochemical controls: photosynthesis from one photon -
David Turell,
2023-07-03, 22:49
- Biochemical controls: photosynthesis in phytoplankton -
David Turell,
2023-06-02, 19:13
- Biochemical controls: photosynthesis in algae -
David Turell,
2023-02-01, 16:03
- Biochemical controls: potassium regulation -
David Turell,
2023-01-30, 23:58
- Biochemical controls: how RNA is supplied and delivered - David Turell, 2023-03-06, 19:09
- Biochemical controls: sight from initial molecule's actions -
David Turell,
2023-03-22, 20:26
- Biochemical controls: specialized retinal synapses -
David Turell,
2023-06-19, 15:56
- Biochemical controls: cell conversion controls -
David Turell,
2023-06-29, 17:19
- Biochemical controls: cell life or death controls - David Turell, 2023-06-30, 15:13
- Biochemical controls: cell conversion controls -
David Turell,
2023-06-29, 17:19
- Biochemical controls: specialized retinal synapses -
David Turell,
2023-06-19, 15:56
- Biochemical controls: intracellular electrical controls -
David Turell,
2022-09-10, 15:54
- Biochemical controls: controlling cell protein output -
David Turell,
2022-05-31, 19:20
- Biochemical controls: plant wound signals - David Turell, 2022-10-22, 16:57