page_title: Free fatty acid receptor 1
section_title: In the pancreas
hierarchical_section_title: Free fatty acid receptor 1 / In the pancreas
caption_attribution_description: English: Simple representation of how FFA1 is linked to increased cytosolic [Ca2+]
context_page_description: Free fatty acid receptor 1, also known as GPR40, is a class A G-protein coupled receptor that in humans is encoded by the FFAR1 gene. It is strongly expressed in the cells of the pancreas and to a lesser extent in the brain. This membrane protein binds free fatty acids, acting as a nutrient sensor for regulating energy homeostasis.
context_section_description: FFA1 is found in highest concentration in Islets of Langerhans, the endocrine portion of the pancreas. Activation of FFA1 results in an increase in cytosolic Ca²⁺ via the phosphoinositide pathway. When a free fatty acid docks on FFA1, the membrane protein becomes activated. This activation causes one of its subunits to dissociate from the receptor, which then activates phospholipase C (PLC) which is found in the cell membrane. PLC in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP₂),which is also in the membrane, to diacyl glycerol (DAG) which stays in the membrane, and inositol 1,4,5-triphosphate (IP₃), which enters the cytosol. IP₃ can then dock on a calcium channel in the endoplasmic reticulum which will facilitate the release of Ca²⁺ into the cytosol.
  The Ca²⁺ that is released then initiates a signal cascade, resulting in the secretion of insulin. A high concentration of glucose in the blood has been found to increase the transcription of the FFA1 gene, which has made these receptors a new target for the treatment of type II diabetes. While fatty acids themselves do not elicit insulin secretion, FFA1 activation increases the amount of insulin being secreted through various linked pathways. It has also been shown that chronic exposure to high amounts of free fatty acids, like on a high fat diet, can impair the function and secretory capacity of pancreatic β-cells.
caption: Simple representation of how FFA1 is linked to increased cytosolic [Ca2+]
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