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An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans
Obesity is a debilitating disease that has become a global epidemic. Although progress is being made, the underlying molecular mechanism by which obesity develops still remains elusive. Recently, we reported that the expression levels of bromodomain-containing protein 7 (BRD7) are significantly reduced in the liver of obese mice. However, it is not clear whether decreased […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00BRD7 deficiency leads to the development of obesity and hyperglycemia
The loss of functional insulin-producing ß-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic ß-cell death and dysfunction; its deficiency restores functional ß-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a ß-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug […]
Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00BCAA catabolism in brown fat controls energy homeostasis through SLC25A44
he fat mass and obesity-associated gene (FTO) encodes an m6A RNA demethylase that controls mRNA processing and has been linked to both obesity and bone mineral density in humans by genome-wide association studies. To examine the role of FTO in bone, we characterized the phenotype of mice lacking Fto globally (FtoKO) or selectively in osteoblasts […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00The RNA demethylase FTO is required for maintenance of bone mass and functions to protect osteoblasts from genotoxic damage
Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental transcription factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00Sox17 is required for endothelial regeneration following inflammation-induced vascular injury
Although human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146 ) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, […]
Metastasis is the major driver of death in patients with cancer. Invasion of surrounding tissues and metastasis have been proposed to initiate following loss of the intercellular adhesion protein, E-cadherin1,2, on the basis of inverse correlations between in vitro migration and E-cadherin levels3. However, this hypothesis is inconsistent with the observation that most breast cancers […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00E-cadherin is required for metastasis in multiple models of breast cancer
Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans
/in PUB-7933 Featured /by Haig DidizianAn insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with […]
BRD7 deficiency leads to the development of obesity and hyperglycemia
/in PUB-7991 Featured /by Haig DidizianObesity is a debilitating disease that has become a global epidemic. Although progress is being made, the underlying molecular mechanism by which obesity develops still remains elusive. Recently, we reported that the expression levels of bromodomain-containing protein 7 (BRD7) are significantly reduced in the liver of obese mice. However, it is not clear whether decreased […]
Neratinib protects pancreatic beta cells in diabetes
/in PUB-8237 Featured /by Haig DidizianThe loss of functional insulin-producing ß-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic ß-cell death and dysfunction; its deficiency restores functional ß-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a ß-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug […]
BCAA catabolism in brown fat controls energy homeostasis through SLC25A44
/in PUB-8171 Featured /by Haig DidizianBranched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes […]
The RNA demethylase FTO is required for maintenance of bone mass and functions to protect osteoblasts from genotoxic damage
/in PUB-8172 Featured /by Haig Didizianhe fat mass and obesity-associated gene (FTO) encodes an m6A RNA demethylase that controls mRNA processing and has been linked to both obesity and bone mineral density in humans by genome-wide association studies. To examine the role of FTO in bone, we characterized the phenotype of mice lacking Fto globally (FtoKO) or selectively in osteoblasts […]
Sox17 is required for endothelial regeneration following inflammation-induced vascular injury
/in PUB-8017 Featured /by Haig DidizianRepair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental transcription factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate […]
GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis
/in PUB-8248 Featured /by Haig DidizianAlthough human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146 ) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, […]
E-cadherin is required for metastasis in multiple models of breast cancer
/in PUB-8187 Featured /by Haig DidizianMetastasis is the major driver of death in patients with cancer. Invasion of surrounding tissues and metastasis have been proposed to initiate following loss of the intercellular adhesion protein, E-cadherin1,2, on the basis of inverse correlations between in vitro migration and E-cadherin levels3. However, this hypothesis is inconsistent with the observation that most breast cancers […]