A5019063918- Pancreatic function and diabetes
- Diabetes and associated disorders
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Immune Cell Function and Interaction
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Estrogen and related hormone effects
- Cytokine Signaling Pathways and Interactions
- Regulation of Appetite and Obesity
- Epigenetics and DNA Methylation
- Muscle metabolism and nutrition
- Peroxisome Proliferator-Activated Receptors
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Tryptophan and brain disorders
- Natural Antidiabetic Agents Studies
- Fibroblast Growth Factor Research
- Biochemical Analysis and Sensing Techniques
- NF-κB Signaling Pathways
- interferon and immune responses
- Inflammatory mediators and NSAID effects
- RNA Research and Splicing
Pennington Biomedical Research Center
2016-2025
Louisiana State University
2025
Immungenetics (Germany)
2022
Louisiana State University System
2019-2021
University of Glasgow
2017
University of Tennessee at Knoxville
2011-2015
University of Maryland Medical Center
2015
University of Maryland, Baltimore
2015
University of Pittsburgh
2009
Deerfield (United States)
2007
Reduced dietary protein intake induces adaptive physiological changes in macronutrient preference, energy expenditure, growth, and glucose homeostasis. We demonstrate that deletion of the FGF21 co-receptor βKlotho (Klb) from brain produces mice are unable to mount a response restriction, an effect is replicated by whole-body FGF21. Mice forced consume low-protein diet exhibit reduced increased resistance diet-induced obesity, but loss signaling completely abrogates response. When given...
FGF21 contributes to the metabolic response dietary protein restriction, and prior data implicate GCN2 as amino acid sensor linking restriction induction. Here, we demonstrate persistent essential role of in restriction. We show that Fgf21 KO mice are fully resistant low (LP)-induced changes food intake, energy expenditure (EE), body weight gain, gene expression for 6 months. Gcn2 recapitulate this phenotype, but LP-induced effects on EE, subsequently begin appear after 14 days diet. delayed...
Dietary protein restriction is increasingly recognized as a unique approach to improve metabolic health, and there increasing interest in the mechanisms underlying this beneficial effect. Recent work indicates that hormone FGF21 mediates effects of young mice. Here we demonstrate increases lifespan, reduces frailty, lowers body weight adiposity, improves physical performance, glucose tolerance, alters various markers within serum, liver, adipose tissue wildtype male Conversely, mice lacking...
Abstract Objective: Internet weight loss programs have become widely available as alternatives to standard treatment, but few data are on their efficacy. This study aimed investigate the effectiveness of a structured behavioral website (VTrim) vs. commercial ( eDiets.com ). Research Methods and Procedures: A randomized, controlled trial was conducted from February 2003 March 2005, in 124 overweight obese subjects ages 18 years older with BMI 25 39.9 kg/m 2 (mean age, 47 ± 9 years; BMI, 32 3...
Diabetes mellitus results from immune cell invasion into pancreatic islets of Langerhans, eventually leading to selective destruction the insulin-producing β-cells. How this process is initiated not well understood. In study, we investigated regulation CXCL1 and CXCL2 genes, which encode proteins that promote migration CXCR2(+) cells, such as neutrophils, toward secreting tissue. Herein, found IL-1β markedly enhanced expression genes in rat β-cell lines, resulted increased secretion each...
To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient ( db/db ). All were monitored for changes body composition, glycemia, total mass. objectively compare diet-induced genetic models obesity, tissue analyses conducted using with similar We found adipose inflammation was present both obesity. In addition, distinct...
SummaryBackgroundProcalcitonin is a rapid response biomarker specific for bacterial infection, which not routinely used in the UK National Health Service. We aimed to assess whether using procalcitonin-guided algorithm would safely reduce duration of antibiotic therapy compared with usual care, C-reactive protein commonly biomarker.MethodsThe BATCH trial was pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled conducted 15 hospitals England and Wales....
Proinflammatory cytokines impact islet β-cell mass and function by altering the transcriptional activity within pancreatic β-cells, producing increases in intracellular nitric oxide abundance synthesis secretion of immunomodulatory proteins such as chemokines. Herein, we report that IL-1β, a major mediator inflammatory responses associated with diabetes development, coordinately reciprocally regulates chemokine insulin secretion. We discovered NF-κB controls increase transcription well...
A reduction in functional β-cell mass leads to both major forms of diabetes; pro-inflammatory cytokines, such as interleukin-1beta (IL-1β) and gamma-interferon (γ-IFN), activate signaling pathways that direct pancreatic death dysfunction. However, the molecular mechanism this context is not well understood. In report, we tested hypothesis individual cellular display characteristic phenotypes allow them be distinguished by precise biochemical metabolic responses occur during stimulus-specific...
The CXCL10 gene encodes a peptide that chemoattracts variety of leukocytes associated with type 1 and 2 diabetes. present study was undertaken to determine the molecular mechanisms required for expression in response IL-1β IFN-γ using rat islets β cell lines. induced promoter activity, whereas combination plus synergistic. Small interfering RNA-mediated suppression NF-κB p65 markedly inhibited ability cytokines induce gene, targeting STAT1 only diminished synergy provided by IFN-γ....
Pancreatic tissue, and islets in particular, are enriched expression of the interleukin-1 receptor type I (IL-1R). Because this enrichment, islet β-cells exquisitely sensitive to IL-1R ligands IL-1α IL-1β, suggesting that signaling through pathway regulates health function β-cells.Herein, we report a targeted deletion pancreatic tissue (IL-1RPdx1-/-) C57BL/6J mice db/db on C57 genetic background. Islet morphology, β-cell transcription factor abundance, de-differentiation marker Aldh1a3 were...
The proinflammatory cytokines IL-1β and IFN-γ decrease functional islet β-cell mass in part through the increased expression of specific genes, such as inducible nitric oxide synthase (iNOS). Dysregulated iNOS protein accumulation leads to overproduction oxide, which induces DNA damage, impairs function, ultimately diminishes cellular viability. However, transcriptional mechanisms underlying cytokine-mediated gene are not completely understood. Herein, we demonstrated that individual...
Glucocorticoids (GCs) are an important class of therapeutic steroids commonly prescribed to treat inflammation and autoimmune disorders. However, long term GC use can lead serious metabolic complications including alterations in insulin sensitivity, resulting increased risk for diabetes. The anti-inflammatory activity stems from GCs binding the glucocorticoid receptor (GR) functioning oppose pro-inflammatory outcomes, while their undesired side effects arise through a variety incompletely...
Obesity is associated with chronic inflammation. Toll-like receptors (TLR) and NOD-like (NLR) are two families of pattern recognition that play important roles in immune response inflammation adipocytes. It has been reported TLR4 TLR2 activation induce proinflammatory changes impair adipocyte differentiation. However, the effects NOD1 NOD2, prominent members NLR, on differentiation have not studied.3T3-L1 human adipose-derived stem cells were tested for presence or absence NOD ligand....
Abstract Type 1 diabetes mellitus (T1DM) results from immune cell‐mediated reductions in function and mass of the insulin‐producing β‐cells within pancreatic islets. While initial trigger(s) that initiates autoimmune process is unknown, there a leukocytic infiltration precedes islet β‐cell death dysfunction. Herein, we demonstrate genes encoding chemokines CXCL9, 10, 11 are primary response also elevated as part inflammatory mouse, rat, human We further established STAT1 participates...
Release of pro-inflammatory cytokines from both resident and invading leukocytes within the pancreatic islets impacts development Type 1 diabetes mellitus. Synthesis secretion chemokine CCL2 β-cells in response to signaling pathways influences immune cell recruitment into islets. Therefore, we investigated positive negative regulatory components controlling expression gene using isolated rat INS-1-derived β-cell lines. We discovered that activation by IL-1β required p65 subunit NF-κB was...
Adaptations in hepatic and skeletal muscle substrate metabolism following acute chronic (6 wk; 5 days/wk; 1 h/day) low-intensity treadmill exercise were tested healthy male C57BL/6J mice. Low-intensity maximizes lipid utilization; therefore, we hypothesized pathways involved would be most robustly affected. Acute nearly depleted liver glycogen immediately postexercise (0 h), whereas triglyceride (TAG) stores increased the early stages after (0–3 h). Also, peroxisome proliferator-activated...
Increased glucose flux generates metabolic signals that control transcriptional programs through poorly understood mechanisms. Previously, we demonstrated a necessity in hepatocytes for c-Myc the regulation of prototypical glucose-responsive gene, L-type pyruvate kinase (L-PK) (Collier JJ, Doan TT, Daniels MC, Schurr JR, Kolls JK, Scott DK. J Biol Chem 278: 6588-6595, 2003). Pancreatic beta-cells have many features common with respect to glucose-regulated gene expression, and present study...