A5014061259- FOXO transcription factor regulation
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Diabetes and associated disorders
- Lipid metabolism and disorders
- Liver Disease Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Diabetes Management and Research
- Adipokines, Inflammation, and Metabolic Diseases
- Heat shock proteins research
- Diet, Metabolism, and Disease
- Birth, Development, and Health
- Diabetes Treatment and Management
- Cholesterol and Lipid Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Atherosclerosis and Cardiovascular Diseases
- Gestational Diabetes Research and Management
- Retinoids in leukemia and cellular processes
- RNA modifications and cancer
- Stroke Rehabilitation and Recovery
- Hormonal Regulation and Hypertension
- RNA Research and Splicing
Children's Hospital of Pittsburgh
2011-2025
University of Pittsburgh
2014-2025
Second Hospital of Shanxi Medical University
2024
Shanxi Medical University
2024
First Affiliated Hospital of GuangXi Medical University
2024
Guangxi Medical University
2024
Kaiser Permanente Tysons Corner Medical Center
2024
Kaiser Permanente
2023
Pittsburg State University
2023
Diabetes Australia
2022
Advanced glycation end products (AGEs), known promoters of diabetic complications, form abundantly in heated foods and are ingested bioreactive forms. To test whether dietary AGEs play a role the progression insulin resistance, C57/BL/KsJ db/db mice were randomly placed for 20 weeks on diet with either low AGE content (LAD) or 3.4-fold higher (high [HAD]), including εN-carboxymethyllysine (CML) methylglyoxal (MG). LAD-fed showed lower fasting plasma levels throughout study (P = 0.01). Body...
Excessive production of triglyceride-rich VLDL is attributable to hypertriglyceridemia. facilitated by microsomal triglyceride transfer protein (MTP) in a rate-limiting step that regulated insulin. To characterize the underlying mechanism, we studied hepatic MTP regulation forkhead box O1 (FoxO1), transcription factor plays key role insulin signaling. In HepG2 cells, expression was induced FoxO1 and inhibited exposure This effect correlated with ability bind stimulate promoter activity....
The apolipoprotein apoC-III plays an important role in plasma triglyceride metabolism. It is predominantly produced liver, and its hepatic expression inhibited by insulin. To elucidate the inhibitory mechanism of insulin expression, we delivered forkhead box O1 (Foxo1) cDNA to hepatocytes adenovirus-mediated gene transfer. Foxo1 stimulated correlated with ability bind consensus site promoter. Deletion or mutation binding abolished response Foxo1-mediated stimulation. Likewise, also mediated...
The apolipoprotein apoC-III plays an important role in plasma triglyceride metabolism. It is predominantly produced liver, and its hepatic expression inhibited by insulin. To elucidate the inhibitory mechanism of insulin expression, we delivered forkhead box O1 (Foxo1) cDNA to hepatocytes adenovirus-mediated gene transfer. Foxo1 stimulated correlated with ability bind consensus site promoter. Deletion or mutation binding abolished response Foxo1-mediated stimulation. Likewise, also mediated...
Successful islet transplantation depends on the infusion of sufficiently large quantities islets, which only ∼30% become stably engrafted. Rapid and adequate revascularization transplanted islets is important for survival function. Delayed insufficient can deprive oxygen nutrients, resulting in cell death early graft failure. To improve revascularization, we delivered human vascular endothelial growth factor (VEGF) cDNA to murine followed by under renal capsule diabetic mice. Diabetic...
Excessive hepatic glucose production is a contributing factor to fasting hyperglycemia in diabetes. Insulin suppresses by inhibiting the expression of two gluconeogenic enzymes, phospho enolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). The forkhead transcription Foxo1 has been implicated as mediator insulin action regulating gluconeogenesis, mutant (Foxo1-Δ256), devoid its carboxyl domain, shown interfere with function inhibit gene cultured cells. To study effect...
OBJECTIVE Macrophages play an important role in the pathogenesis of insulin resistance via production proinflammatory cytokines. Our goal is to decipher molecular linkage between cytokine and macrophages. RESEARCH DESIGN AND METHODS We determined profiles cultured macrophages identified interleukin (IL)-1β gene as a potential target FoxO1, key transcription factor that mediates action on expression. studied mechanism by which FoxO1 insulin-dependent regulation IL-1β expression correlated...
Successful islet transplantation depends on the infusion of sufficiently large quantities islets, but only a fraction transplanted islets can survive and become engrafted, yet underlying mechanism remains unclear. In this study, we examined effect sirolimus, key component immunosuppressive regimen in clinical transplantation, engraftment function. To distinguish sirolimus immune rejection from its engraftment, used syngeneic model. Diabetic mice were with 250 under renal capsule, followed by...
Hypertriglyceridemia is the most common lipid disorder in obesity and type 2 diabetes. It results from increased production and/or decreased clearance of triglyceride-rich lipoproteins. To better understand pathophysiology hypertriglyceridemia, we studied hepatic regulation triglyceride metabolism by activating transcription factor 4 (ATF4), a member basic leucine zipper-containing protein subfamily. We determined effect ATF4 on Atf4−/− mice fed regular chow or provided with free access to...
Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied ability forkhead box O6 (FoxO6) mediate action on gluconeogenesis and its contribution metabolism.We characterized FoxO6 metabolism cultured hepatocytes rodent models dietary obesity, resistance, or insulin-deficient We determined genetically modified mice with gain- versus...
FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. Increased activity is associated with reduced ability to regulate glucose production. However, underlying mechanism and physiology remain unknown. We studied metabolism normal vs. insulin-resistant liver under fed fasting conditions. gain function, as a result adenovirus-mediated or transgenic expression, augmented gluconeogenesis, accompanied by decreased glycogen content increased fat deposition liver....
Abstract β-Cell compensation is an essential mechanism by which β-cells increase insulin secretion for overcoming resistance to maintain euglycemia in obesity. Failure of compensate contributes insufficiency and overt diabetes. To understand the β-cell compensation, we characterized role forkhead box O1 (FoxO1) mice under physiological pathological conditions. FoxO1 a key transcription factor that serves as nutrient sensor integrating signaling cell metabolism, growth, proliferation. We...
Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). results from abnormal macrophage activation. We found that FoxO1 links overnutrition hepatic by regulating polarization and was upregulated in macrophages, correlating with inflammation, steatosis, fibrosis mice patients NASH. Myeloid cell conditional knockout skewed proinflammatory M1 antiinflammatory M2 phenotype, accompanied a reduction infiltration liver. These effects...
The yeast Zip1 protein is a component of the central region synaptonemal complex (SC). predicted to form an α-helical coiled coil, flanked by globular domains at NH2 and COOH termini. Immunogold labeling with domain-specific anti–Zip1 antibodies demonstrates that NH2-terminal domain located in middle SC, whereas COOH-terminal embedded lateral elements complex. Previous studies have shown overproduction results assembly two types aggregates, polycomplexes networks, are unassociated chromatin....
High-fructose consumption is associated with insulin resistance and diabetic dyslipidemia, but the underlying mechanism unclear. We show in hamsters that high-fructose feeding stimulated forkhead box O1 (FoxO1) production promoted its nuclear redistribution liver, correlating augmented apolipoprotein C-III (apoC-III) impaired triglyceride metabolism. upregulated peroxisome proliferator-activated receptor-gamma coactivator-1beta sterol regulatory element binding protein-1c expression,...
Purpose of review This summarizes recent research implicating Forkhead box (Fox)O1, a key transcription factor in glucose metabolism, the regulation hepatic lipid metabolism. Insulin dysregulation leading to hypertriglyceridemia is associated with increased VLDL secretion. FoxO1 integrated action other regulatory factors The role defined context controversies. Recent findings regulates microsomal triglyceride transfer protein and apolipoprotein (apo)CIII involved assembly postsecretory...
In this study, we determined the molecular mechanisms whereby forkhead transcription factor Foxo1, a key downstream signaling molecule of insulin-like growth 1 (IGF1)/insulin actions, regulates Runx2 activity and expression mouse osteocalcin gene 2 (Bglap2) in osteoblasts vitro. We showed that Foxo1 inhibited Runx2-dependent transcriptional mRNA Bglap2 promoter MC-4 preosteoblasts. Co-immunoprecipitation assay physically interacted with via its C-terminal region or when co-expressed COS-7...
Inducible nitric-oxide synthase (iNOS), a major mediator of inflammation, plays an important role in obesity-induced insulin resistance. Inhibition iNOS by gene disruption or pharmacological inhibitors reverses ameliorates resistance skeletal muscle and liver mice. It is unknown, however, whether increased expression sufficient to cause vivo. To address this issue, we generated liver-specific transgenic (L-iNOS-Tg) mice, where the transgene, iNOS, regulated under mouse albumin promoter....
Apolipoproteins (apo) are constituents of lipoproteins crucial for lipid homeostasis. Aberrant expression apolipoproteins is associated with metabolic abnormalities. Here we characterized apolipoprotein D (apoD) in triglyceride metabolism. Unlike canonical that mainly produced the liver, apoD an atypical broad tissue distribution. We show circulating present HDL and, to a lesser extent, LDL and VLDL its plasma levels were reduced db/db mice visceral obesity altered Elevated production,...
Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms chronic diseases closely associated with obesity and insulin resistance; deficient growth hormone (GH) action in has been implicated as a mechanism. Here, we investigated evolution NAFLD aged mice liver-specific GHR deletion.We examined glucose tolerance, responsiveness, lipid profiles male (44-50 weeks) GHRLD. We performed proteomics analysis, pathway-based Superarray assay, well quantitative RT-PCR to gain molecular...