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Catherine B MarElia, Melanie N Kuehl, Tiffany A Shemwell, Amy C Alman, Brant R Burkhardt
Aim: PANcreatic-DERived factor (PANDER, FAM3B) is a novel hormone that regulates glucose levels via interaction with both the endocrine pancreas and liver. Prior studies examining PANDER were primarily conducted in murine models or in vitro but little is known regarding the circulating concentration of PANDER in humans, especially with regard to the association of type 2 diabetes (T2D) or overall glycemic regulation. To address this limitation, we performed a cross-sectional analysis of circulating serum PANDER concentration in association with other hormones that serve as either markers of insulin resistance (insulin and adiponectin) or to metabolic parameters of glycemic control such as fasting HbA1c and blood glucose (FBG)...
March 2018: Journal of Clinical & Translational Endocrinology
Paula Maciel-Silva, Izabela Caldeira, Icaro de Assis Santos, Ana Claudia Oliveira Carreira, Flavia Ramos Siqueira, Eliane Antonioli, Anna Carla Goldberg, José Ernesto Belizário, Humberto Miguel Garay-Malpartida
BACKGROUND: FAM3B/PANDER is a novel cytokine-like protein that induces apoptosis in insulin-secreting beta-cells. Since in silico data revealed that FAM3B can be expressed in prostate tumors, we evaluated the putative role of this cytokine in prostate tumor progression. METHODS: FAM3B expression was analyzed by quantitative PCR in tumor tissue clinical samples and prostate tumor cell lines. Culture growth and viability of DU145 cell line were evaluated after treatment with either exogenous FAM3B protein obtained from conditioned media (CM) of 293 T cells overexpressing FAM3B or a recombinant FAM3B protein produced in a bacterial host...
January 22, 2018: BMC Cancer
Xiaoyan Zhang, Weili Yang, Junpei Wang, Yuhong Meng, Youfei Guan, Jichun Yang
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...
April 2018: Metabolism: Clinical and Experimental
Haoyu Wang, Fadong Yu, Zhuo Zhang, Yuanyuan Hou, Weiping Teng, Zhongyan Shan, Yaxin Lai
AIMS/INTRODUCTION: Member B of the family with sequence similarity 3 (FAM3B), also known as pancreatic-derived factor, is mainly synthesized and secreted by islet β-cells, and plays a role in abnormal metabolism of glucose and lipids. However, the prospective association of FAM3B with metabolic disorders remains unclear. The present study aimed to reveal the predictive relationship between pancreas-specific cytokine and metabolic syndrome (MetS). MATERIALS AND METHODS: A total of 210 adults (88 men and 122 women) without MetS, aged between 40 and 65 years, were recruited and received a comprehensive health examination...
November 27, 2017: Journal of Diabetes Investigation
Wenxiang Zhang, Siyu Chen, Zhao Zhang, Chen Wang, Chang Liu
The proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role during the development of cardiovascular diseases (CVDs). While many factors potentially contribute to the abnormal activation of VSMCs, hyperglycemia is generally believed to be a major causative factor. On the other hand, FAM3B (named PANDER for its secretory form) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. FAM3B is co-secreted with insulin from the β-cell upon glucose stimulation and regulates glucose homeostasis...
May 23, 2017: Scientific Reports
Shunsuke Nakajima, Hiroki Tanaka, Koji Sawada, Hidemi Hayashi, Takumu Hasebe, Masami Abe, Chitomi Hasebe, Mikihiro Fujiya, Toshikatsu Okumura
BACKGROUND AND AIM: Some single-nucleotide polymorphisms (SNPs) are associated with the development of non-alcoholic fatty liver disease (NAFLD). As one of the genetic factors, PNPLA3 rs738409 (I148M) is important to associate with pathogenesis of NAFLD. Because other SNPs remain unclear in Japan, we performed a high-throughput sequencing that targeted more than 1000 genes to identify a novel genetic variant in Japanese patients with NAFLD. METHODS: The present study in 36 NAFLD patients and 27 healthy volunteers was performed...
January 2018: Journal of Gastroenterology and Hepatology
Xinjian Peng, Enquan Xu, Weiwei Liang, Xiaolei Pei, Dixin Chen, Danfeng Zheng, Yang Zhang, Can Zheng, Pingzhang Wang, Shaoping She, Yan Zhang, Jing Ma, Xiaoning Mo, Yingmei Zhang, Dalong Ma, Ying Wang
The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members FAM3A, FAM3B, FAM3C and FAM3D. In this study, we found that FAM3D strongly chemoattracted human peripheral blood neutrophils and monocytes. To identify the FAM3D receptor, we used chemotaxis, receptor internalization, Ca(2+) flux and radioligand-binding assays in FAM3D-stimulated HEK293 cells that transiently expressed formyl peptide receptor (FPR)1 or FPR2 to show that FAM3D was a high affinity ligand of these receptors, both of which were highly expressed on the surface of neutrophils, and monocytes and macrophages...
May 1, 2016: Journal of Cell Science
Xiaoling Jiang, Chunhong Liu, Tao Yu, Li Zhang, Kai Meng, Zhuo Xing, Pavel V Belichenko, Alexander M Kleschevnikov, Annie Pao, Jennifer Peresie, Sarah Wie, William C Mobley, Y Eugene Yu
Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam3b/Mx2. We first confirmed the importance of the Cbr1-Fam3b region using compound mutant mice, which carry a duplication spanning the entire human chromosome 21 orthologous region on mouse chromosome 16 [Dp(16)1Yey] and Ms1Rhr...
November 15, 2015: Human Molecular Genetics
Whitney A Ratliff, Mark G Athanason, Alicia C Chechele, Melanie N Kuehl, Amanda M Fernandez, Catherine B MarElia, Brant R Burkhardt
PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis...
September 15, 2015: Molecular and Cellular Endocrinology
Xiaoqing Mo, Chijiao Yang, Xuelan Wang, Brant R Burkhardt, Yangbin Li, Haipeng Xia, Xiaopei Cao
OBJECTIVE: Pancreatic-derived factor (PANDER, also named as FAM3B) is secreted by pancreatic α and β cells. Increasing evidence suggests that it may serve a hormonal function related to glycemic and lipid metabolism. In this study, we investigated the effects of PANDER overexpression on hepatic and adipose triglyceride metabolism in high-fat diet-fed male C57BL/6 mice. METHODS: PANDER overexpression was achieved by tail-vein injection of recombinant Ad-PANDER and Ad-GFP injected mice served as a control...
2015: PloS One
Shari L Moak, Grace C Dougan, Catherine B MarElia, Whitney A Danse, Amanda M Fernandez, Melanie N Kuehl, Mark G Athanason, Brant R Burkhardt
Pancreatic-derived factor (PANDER; also known as FAM3B) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. PANDER has been hypothesized to regulate fasting and fed glucose homeostasis, hepatic lipogenesis and insulin signaling, and to serve a potential role in the onset or progression of type 2 diabetes (T2D). Despite having potentially pivotal pleiotropic roles in glycemic regulation and T2D, there has been limited generation of stable animal models for the investigation of PANDER function, and there are no models on well-established genetic murine backgrounds for T2D...
November 2014: Disease Models & Mechanisms
Qiaoyi Liang, Xiaotian Yao, Senwei Tang, Jingwan Zhang, Tung On Yau, Xiaoxing Li, Ceen-Ming Tang, Wei Kang, Raymond W M Lung, Jing Woei Li, Ting Fung Chan, Rui Xing, Youyong Lu, Kwok Wai Lo, Nathalie Wong, Ka Fai To, Chang Yu, Francis K L Chan, Joseph J Y Sung, Jun Yu
BACKGROUND & AIMS: The mechanisms by which Epstein-Barr virus (EBV) contributes to the development of gastric cancer are unclear. We investigated EBV-associated genomic and epigenomic variations in gastric cancer cells and tumors. METHODS: We performed whole-genome, transcriptome, and epigenome sequence analyses of a gastric adenocarcinoma cell line (AGS cells), before and after EBV infection. We then looked for alterations in gastric tumor samples, with (n = 34) or without (n = 100) EBV infection, collected from patients at the Prince of Wales Hospital, Chinese University of Hong Kong (from 1998 through 2004), or the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (from 1999 through 2006)...
December 2014: Gastroenterology
Claudia E Robert-Cooperman, Grace C Dougan, Shari L Moak, Mark G Athanason, Melanie N Kuehl, Harris Bell-Temin, Stanley M Stevens, Brant R Burkhardt
PANcreatic-DERived factor (PANDER, FAM3B) is a novel protein that is highly expressed within the endocrine pancreas and to a lesser degree in other tissues. Under glucose stimulation, PANDER is co-secreted with insulin from the β-cell. Despite prior creation and characterization of acute hepatic PANDER animal models, the physiologic function remains to be elucidated from pancreas-secreted PANDER. To determine this, in this study, a transgenic mouse exclusively overexpressing PANDER from the endocrine pancreas was generated...
March 2014: Journal of Endocrinology
Bo Gao, Wang Sun, Xianqi Wang, Xu Jia, Biao Ma, Yu Chang, Weihui Zhang, Dongbo Xue
Bone marrow endothelial cells (BMECs) are important components of the hematopoietic microenvironment in bone marrow, and they can secrete several types of cytokines to regulate the functions of hematopoietic stem/progenitor cells. To date, it is unknown whether BMECs undergo functional changes and lead to hematopoietic abnormalities in cases of liver cirrhosis (LC). In the present study, whole genome microarray analysis was carried out to detect differentially expressed genes in human BMECs treated for 48 h with medium supplemented with 20% pooled sera from 26 patients with LC or 10 healthy volunteers as the control group...
November 2013: International Journal of Molecular Medicine
Li Zhang, Kai Meng, Xiaoling Jiang, Chunhong Liu, Annie Pao, Pavel V Belichenko, Alexander M Kleschevnikov, Sheena Josselyn, Ping Liang, Ping Ye, William C Mobley, Y Eugene Yu
Trisomy 21 (Down syndrome, DS) is the most common genetic cause of developmental cognitive deficits, and the so-called Down syndrome critical region (DSCR) has been proposed as a major determinant of this phenotype. The regions on human chromosome 21 (Hsa21) are syntenically conserved on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. DSCR is conserved between the Cbr1 and Fam3b genes on Mmu16. Ts65Dn mice carry three copies of ∼100 Hsa21 gene orthologs on Mmu16 and exhibited impairments in the Morris water maze and hippocampal long-term potentiation (LTP)...
February 1, 2014: Human Molecular Genetics
Jichun Yang, Youfei Guan
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...
August 2013: Journal of Gastroenterology and Hepatology
Patrik Johansson, Jenny Bernström, Tracy Gorman, Linda Oster, Stefan Bäckström, Fritz Schweikart, Bingze Xu, Yafeng Xue, Lovisa Holmberg Schiavone
The FAM3 superfamily is predicted to contain classical four-helix bundle cytokines, featuring a typical up-up-down-down fold. Two members of FAM3 have been extensively studied. FAM3B PANDER has been shown to regulate glucose homeostasis and β cell function, whereas the homologous FAM3C ILEI has been shown to be involved in epithelial-mesenchymal transition and cancer. Here, we present a three-dimensional structure of a FAM3 protein, murine PANDER. Contrary to previous suggestions, PANDER exhibits a globular β-β-α fold...
February 5, 2013: Structure
Meian He, Chen Wu, Jianfeng Xu, Huan Guo, Handong Yang, Xiaomin Zhang, Jielin Sun, Dianke Yu, Li Zhou, Tao Peng, Yunfeng He, Yong Gao, Jing Yuan, Qifei Deng, Xiayun Dai, Aihua Tan, Yingying Feng, Haiying Zhang, Xinwen Min, Xiaobo Yang, Jiang Zhu, Kan Zhai, Jiang Chang, Xue Qin, Wen Tan, Yanling Hu, Mingjian Lang, Sha Tao, Yuanfeng Li, Yi Li, Junjie Feng, Dongfeng Li, Seong-Tae Kim, Shijun Zhang, Hongxing Zhang, S Lilly Zheng, Lixuan Gui, Youjie Wang, Sheng Wei, Feng Wang, Weimin Fang, Yuan Liang, Yun Zhai, Weihong Chen, Xiaoping Miao, Gangqiao Zhou, Frank B Hu, Dongxin Lin, Zengnan Mo, Tangchun Wu
OBJECTIVE: Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers. DESIGN: We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals...
January 2014: Gut
Haiwei Mou, Zongmeng Li, Pengle Yao, Shu Zhuo, Wei Luan, Bo Deng, Lihua Qian, Mengmei Yang, Hong Mei, Yingying Le
FAM3B, also named PANDER, is a cytokine-like protein identified in 2002. Previous studies showed that FAM3B regulates glucose and lipid metabolism through interaction with liver and endocrine pancreas. FAM3B is also expressed by other tissues but its basic function is unclear. In this study, we found that FAM3B was expressed in mouse colon, intestine, liver and lung tissues and multiple types of cell lines, including murine pancreatic β-cell (Min6), microglia (N9) and muscle cell (C2C12); human colon cancer cells (HCT8, HCT116, HT29), hepatocyte (HL-7702), hepatocellular carcinoma cell (SMMC-7721) and lung carcinoma cell (A549)...
March 2013: International Journal of Biochemistry & Cell Biology
Zongmeng Li, Haiwei Mou, Ting Wang, Jing Xue, Bo Deng, Lihua Qian, Ye Zhou, Wanghua Gong, Ji Ming Wang, Guohao Wu, Cheng-Fu Zhou, Jing Fang, Yingying Le
FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here we found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3B-258 in colon cancer cells downregulated adhesion proteins, upregulated Slug and Cdc42, promoted cell migration and invasion in vitro and metastasis in nude mice...
January 28, 2013: Cancer Letters
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