Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis (fatty liver) and nonalcoholic steatohepatitis to fibrosis and cirrhosis. NAFLD has become the leading cause of chronic liver diseases as well as liver-related morbidity and mortality worldwide. NAFLD is also associated with increased risk of cardiovascular diseases, hyperlipidemia, and type 2 diabetes. Insulin resistance in adipose tissues and the liver plays crucial roles in the progression of NAFLD. The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members designated FAM3A, FAM3B, FAM3C, and FAM3D, respectively. Increasing evidence suggests that the FAM3 gene family members are involved in the pathogenesis of NAFLD. In particular, FAM3B, also called pancreatic-derived factor, is an important regulator of glucose and lipid metabolism. In obesity status, increased expression and secretion of FAM3B in pancreatic islets and liver may induce lipid accumulation in the liver via the induction of hepatic insulin resistance and lipogenesis. FAM3A and FAM3D may also participate in the regulation of lipid and energy metabolism. In this brief review, we discussed the latest findings regarding the role of FAM3 gene family members, in particular FAM3B, in the pathogenesis of NAFLD.
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PMID:Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease. 2385 4

FAM3C is a member of the family with sequence similarity 3 (FAM3) gene family, and this study determined its role and mechanism in regulation of hepatic glucose/lipid metabolism. In obese diabetic mice, FAM3C expression was reduced in the liver, and hepatic FAM3C restoration improved insulin resistance, hyperglycemia, and fatty liver. FAM3C overexpression increased the expression of heat shock factor 1 (HSF1), calmodulin (CaM), and phosphorylated protein kinase B (Akt) and reduced that of gluconeogenic and lipogenic genes in diabetic mouse livers with the suppression of gluconeogenesis and lipid deposition. In cultured hepatocytes, FAM3C overexpression upregulated HSF1 expression, which elevated CaM protein level by inducing CALM1 transcription to activate Akt in a Ca2+- and insulin-independent manner. Furthermore, FAM3C overexpression promoted nuclear exclusion of FOXO1 and repressed gluconeogenic gene expression and gluconeogenesis in a CaM-dependent manner in hepatocytes. Hepatic HSF1 overexpression activated the CaM-Akt pathway to repress gluconeogenic and lipogenic gene expression and improve hyperglycemia and fatty liver in obese diabetic mice. In conclusion, the FAM3C-HSF1-CaM-Akt pathway plays important roles in regulating glucose and lipid metabolism in hepatocytes independent of insulin and calcium. Restoring hepatic FAM3C expression is beneficial for the management of type 2 diabetes and fatty liver.
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PMID:Hepatic Activation of the FAM3C-HSF1-CaM Pathway Attenuates Hyperglycemia of Obese Diabetic Mice. 2824 89

Non-alcoholic fatty liver disease (NAFLD) and diabetes are severe public health issues worldwide. The Family with sequence similarity 3 (FAM3) gene family consists of four members designated as FAM3A, FAM3B, FAM3C and FAM3D, respectively. Recently, there had been increasing evidence that FAM3A, FAM3B and FAM3C are important regulators of glucose and lipid metabolism. FAM3A expression is reduced in the livers of diabetic rodents and NAFLD patients. Hepatic FAM3A restoration activates ATP-P2 receptor-Akt and AMPK pathways to attenuate steatosis and hyperglycemia in obese diabetic mice. FAM3C expression is also reduced in the liver under diabetic condition. FAM3C is a new hepatokine that activates HSF1-CaM-Akt pathway and represses mTOR-SREBP1-FAS pathway to suppress hepatic gluconeogenesis and lipogenesis. In contrast, hepatic expression of FAM3B, also called PANDER, is increased under obese state. FAM3B promotes hepatic lipogenesis and gluconeogenesis by repressing Akt and AMPK activities, and activating lipogenic pathway. Under obese state, the imbalance among hepatic FAM3A, FAM3B and FAM3C signaling networks plays important roles in the pathogenesis of NAFLD and type 2 diabetes. This review briefly discussed the latest research progress on the roles and mechanisms of FAM3A, FAM3B and FAM3C in the regulation of hepatic glucose and lipid metabolism.
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PMID:FAM3 gene family: A promising therapeutical target for NAFLD and type 2 diabetes. 2922 90