{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FAM3B, also known as pancreatic‐derived factor (PANDER), is a cytokine‐like protein that is predominantly expressed in the pancreatic islets and is closely associated with insulin secretory granules. In normal physiology, FAM3B is secreted by β‐cells in a glucose‐responsive manner and appears to be co‐released with insulin, thereby contributing to the regulation of glucose homeostasis. Specifically, FAM3B modulates β‐cell function by inhibiting basal insulin secretion and, when overexpressed, can trigger apoptosis through caspase‐mediated pathways. The promoter activity and secretion of FAM3B are regulated by multiple intracellular signaling cascades—including Ca²⁺–PKA–ERK1/2, Ca²⁺–PKC, and transcription factors such as CREB and PDX‐1—underscoring its role in β‐cell physiology and survival (1)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its autocrine actions within the endocrine pancreas, FAM3B exerts endocrine effects on the liver. It binds to liver membranes and impairs insulin receptor signaling, which ultimately promotes hepatic insulin resistance and enhances gluconeogenic gene expression. These actions contribute to increased hepatic glucose output and fasting hyperglycemia, thereby linking FAM3B to the development of metabolic dysfunction and features of the metabolic syndrome (2).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond metabolic regulation, FAM3B has been implicated in cancer biology. Alternative splicing (e.g. the non‐secretory isoform FAM3B‐258) and overexpression in certain tumors—such as colon cancer and esophageal squamous cell carcinoma—have been associated with enhanced tumor cell survival, migration, invasion and metastasis. In these settings, FAM3B appears to modulate key signaling pathways (for example, the Akt–MDM2–p53 cascade) to promote cell survival and resistance to apoptosis (3).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, FAM3B/PANDER functions as a multifaceted mediator: within the pancreas it modulates insulin secretion and β‐cell viability; in the liver it augments gluconeogenesis and contributes to insulin resistance; and in certain cancers, altered FAM3B expression supports tumor progression through pro‐survival signaling. These diverse roles position FAM3B as an important link between endocrine regulation, metabolic homeostasis, and disease pathology.\n (1,2,3)\n "}]}, {"type": "t", "text": "\n \n <ol>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n </li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n </li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n </li>\n </ol>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuan Zhu, Gang Xu, Arun Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning, expression, and initial characterization of a novel cytokine-like gene family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/geno.2002.6816"}], "href": "https://doi.org/10.1006/geno.2002.6816"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12160727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12160727"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaopei Cao, Jichun Yang, Brant R Burkhardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of overexpression of pancreatic derived factor (FAM3B) in isolated mouse islets and insulin-secreting betaTC3 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00113.2005"}], "href": "https://doi.org/10.1152/ajpendo.00113.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15928025"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15928025"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jichun Yang, Zhiyong Gao, Claudia E Robert, et al. 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