A5049426852- Pancreatic function and diabetes
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Birth, Development, and Health
- Diet, Metabolism, and Disease
- FOXO transcription factor regulation
- Diet and metabolism studies
- Pancreatic and Hepatic Oncology Research
- Diabetes Treatment and Management
- Connective Tissue Growth Factor Research
- Congenital heart defects research
- Adipose Tissue and Metabolism
- Gestational Diabetes Research and Management
- Liver Disease Diagnosis and Treatment
- Obesity, Physical Activity, Diet
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Pancreatitis Pathology and Treatment
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Eicosanoids and Hypertension Pharmacology
- Pharmacogenetics and Drug Metabolism
- Fatty Acid Research and Health
Vanderbilt University Medical Center
2016-2025
Vanderbilt University
2015-2024
VA Tennessee Valley Healthcare System
2012-2024
Tennessee Valley Authority
2015-2024
Nashville Oncology Associates
2012-2020
Valley Health System
2019
Tennessee Department of Health
2015
Immunovaccine (Canada)
2015
University of Pennsylvania
2014
Nashville VA Medical Center
2011-2014
Phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) is typically associated with stress responses and causes a reduction in protein synthesis. However, we found high phosphorylated eIF-2 alpha[P]) levels nonstressed pancreata mice. Administration glucose stimulated rapid dephosphorylation alpha. Among the four kinases present mammals, PERK most highly expressed pancreas, suggesting that it may be responsible for alpha[P] therein. We describe Perk knockout mutation Pancreata...
To investigate molecular mechanisms controlling islet vascularization and revascularization after transplantation, we examined pancreatic expression of three families angiogenic factors their receptors in differentiating endocrine cells adult islets. Using intravital lectin labeling, demonstrated that development microvasculature establishment blood flow occur concomitantly with morphogenesis. Our genetic data indicate vascular endothelial growth factor (VEGF)-A is a major regulator...
Complete lack of transcription factor PDX-1 leads to pancreatic agenesis, whereas heterozygosity for mutations has been recently noted in some individuals with maturity-onset diabetes the young (MODY) and type 2 diabetes. To determine how alterations affect islet function, we examined insulin secretion physiology mice one allele inactivated. PDX-1+/− had a normal fasting blood glucose content but impaired tolerance secreted less during testing. The expression transporter islets from...
OBJECTIVE Conditional gene targeting has been extensively used for in vivo analysis of function β-cell biology. The objective this study was to examine whether mouse transgenic Cre lines, mediate β-cell– or pancreas-specific recombination, also drive expression the brain. RESEARCH DESIGN AND METHODS Transgenic lines driven by Ins1, Ins2, and Pdx1 promoters were bred R26R reporter strains. activity assessed β-galactosidase yellow fluorescent protein pancreas Endogenous monitored using...
The mammalian homeobox gene pdx-1 is expressed in pluripotent precursor cells the dorsal and ventral pancreatic bud duodenal endoderm, which will produce pancreas rostral duodenum. In adult, pdr-1 principally within insulin-secreting islet beta of epithelium. Our objective this study was to localize sequences mouse mediating selective expression islet. Studies transgenic mice a genomic fragment from kb -4.5 +8.2 used drive beta-galactosidase reporter showed that control sufficient for...
Pancreatic islet transplantation is an emerging therapy for type 1 diabetes. To survive and function, transplanted islets must revascularize because isolation severs arterial venous connections; the current paradigm that revascularization originates from transplant recipient. Because isolated retain intraislet endothelial cells, we determined whether these cells contribute to using a murine model with tagged (lacZ knock-in Flk-1/VEGFR2 gene) human islets. At 3–5 weeks after beneath renal...
Abstract: Astrocytes play a central role in manganese (Mn) regulation the CNS. Using primary astrocyte cultures from neonatal rat brains, these studies demonstrate specific highaffinity transport system for Mn 2+ . Saturation kinetics are clearly indicated by both l/ s versus plots ( K m = 0.30 ± 0.03 μMM; V max 0.02 nmol/mg of protein/min) and v [ ]. Several divalent cations (Co 2 , Zn Pb ) failed to inhibit initial rate 54 uptake. In contrast, extracellular Ca at 10 μM decreased Exchange...
OBJECTIVE The objectives of the study were to determine whether cell cycle transcription factor, FoxM1, is required for glucose homeostasis and β-cell mass expansion in maternal islets during pregnancy FoxM1 essential placental lactogen (PL)-induced proliferation. RESEARCH DESIGN AND METHODS β-Cell mass, proliferation, assessed virgin, pregnant, postpartum mice with a pancreas-wide Foxm1 deletion (FoxM1Δpanc). Wild-type cultured or without PL examined induction. Transgenic overexpressing...
Both short- (1 wk) and long-term (2-12 mo) high-fat diet (HFD) studies reveal enhanced β-cell mass due to increased proliferation. β-Cell proliferation following HFD has been postulated occur in response insulin resistance; however, whether can induce independent of resistance controversial. To examine the kinetics HFD-induced its correlation with resistance, we placed 8-wk-old male C57Bl/6J mice on for different lengths time assayed following: glucose tolerance, secretion glucose, mass, We...
Tamoxifen (Tm)-inducible Cre recombinases are widely used to perform gene inactivation and lineage tracing studies in mice. Although the efficiency of inducible Cre-loxP recombination can be easily evaluated with reporter strains, precise length time that Tm induces nuclear translocation CreERTm subsequent a target allele is not well defined, difficult assess. To better understand timeline activity vivo, we developed bioassay which pancreatic islets Tm-inducible (from Pdx1PB-CreERTm;R26RlacZ...
To identify potential transactivators ofpdx-1, we sequenced approximately 4.5 kilobases of the 5′ promoter region human and chicken homologs, assuming that sequences conserved with mouse gene would contain criticalcis-regulatory elements. The associated hypersensitive site 1 (HSS1) represented principal area homology within which three subdomains were apparent: I (−2694 to −2561 base pairs (bp)), II (−2139 −1958 bp), III (−1879 −1799 bp). identities between chicken/human genes are very high,...
Pdx1 ( IPF-1 in humans, which is altered MODY-4 ) essential for pancreas development and mature β-cell function. expressed dynamically within the developing foregut, but how its expression characteristics are linked to various steps of organ specification, differentiation, function unknown. Deletion a conserved enhancer region (Area I-II-III) from produced hypomorphic allele Δ I-II-III with timing level expression, was studied combination wild-type protein-null alleles. Lineage labeling...
The FoxM1 transcription factor is highly expressed in proliferating cells and activates several cell cycle genes, although its requirement appears to be limited certain tissue types. Embryonic hepatoblast-specific inactivation of Foxm1 results a dramatic reduction liver outgrowth subsequent late gestation lethality, whereas adult impairs regeneration after partial hepatectomy. These prompted us examine whether functions similarly embryonic the pancreas beta-cell proliferation adult. We found...