A5005448345- Diabetes and associated disorders
- Pancreatic function and diabetes
- Hormonal Regulation and Hypertension
- Diabetes Management and Research
- Immune Cell Function and Interaction
- Electrolyte and hormonal disorders
- Atherosclerosis and Cardiovascular Diseases
- Retinal Diseases and Treatments
- Viral Infections and Immunology Research
- Vitamin K Research Studies
- Apelin-related biomedical research
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Trace Elements in Health
- Immunodeficiency and Autoimmune Disorders
- Cardiac Fibrosis and Remodeling
- Vitamin C and Antioxidants Research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Eicosanoids and Hypertension Pharmacology
- Metabolism, Diabetes, and Cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
University of Tennessee Health Science Center
2016-2025
University of Tennessee at Knoxville
2001-2025
Memphis VA Medical Center
2000-2019
Gainesville Obstetrics & Gynecology
2018
Palm Beach Neurology
2018
Breakthrough T1D
2016
Diabetes Australia
2003-2013
Veterans Health Administration
2004-2009
Ducks Unlimited
1999-2005
Jackson Laboratory
1992-1997
Human pancreatic beta cells may be complicit in their own demise type 1 diabetes, but how this occurs remains unclear. One potentially contributing factor is hyperexpression of HLA class I antigens. This was first described approximately 30 years ago, has never been fully characterised and recently challenged as artefactual. Therefore, we investigated expression at the protein RNA levels pancreases from three cohorts patients with diabetes. The principal aims were to consider whether...
Abstract Aims/hypothesis The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of samples collected date. aim current work was examine presence enterovirus lymphoid without Methods We analysed pancreas, spleen, pancreatic lymph nodes duodenum following groups: (1) diabetes ( n =71) =35) or =36) insulin-containing islets; (2) single...
Background— Aldosteronism may account for oxi/nitrosative stress, a proinflammatory phenotype, and wasting in congestive heart failure. We hypothesized that aldosterone/1% NaCl treatment (ALDOST) rats enhances Ca 2+ Mg excretion leads to systemic effects, including bone loss. Methods Results— At 1, 2, 4, 6 weeks of ALDOST, we monitored excretion, ionized [Ca ] o [Mg , parathyroid hormone α 1 -antiproteinase activity plasma, mineral density, strength, content peripheral blood mononuclear...
Previous results indicate the presence of an interferon (IFN) signature in type 1 diabetes (T1D), capable inducing chronic inflammation and compromising b cell function. Here, we determined expression IFN response markers MxA, PKR, HLA-I islets autoantibody-positive T1D donors. We found that these can be coexpressed same islet, are more abundant insulin-containing islets, highly expressed with insulitis, their levels correlated enteroviral protein VP1. The was associated down-regulation...
Abstract Pancreatic β-cells are prone to endoplasmic reticulum (ER) stress due their role in insulin secretion. They require sustainable and efficient adaptive responses cope with this stress. Whether episodes of chronic directly compromise β-cell identity is unknown. We show here under reversible, conditions undergo transcriptional translational reprogramming associated impaired expression regulators function identity. Upon recovery from stress, regain function, indicating a high degree...
MHC class II alleles clearly contribute a primary genetic component of susceptibility to autoimmune insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. However, IDDM does not occur NOD mice made I-deficient by functionally inactivated beta2-microglobulin allele (beta2m(null)). In the present study beta2m(null) mutation was used examine relative contributions I and II-dependent T cell responses for initiating pancreatic beta destruction Splenocytes from donors...
Intrathymic transplantation of syngeneic islets into adolescent NOD/Lt mice was performed to establish whether the thymus would serve as an immunoprivileged site for β-cell engraftment, and this treatment prevent development diabetes by eliciting tolerance islet antigens. injection cells from 200 NOD 4-wk-old female produced a significant reduction in severity insulitis at 24 wk age. Furthermore, strongly suppressed (11% incidence) compared with controls (100% incidence). Both histology...
The quantity and activation state of adipose tissue macrophages (ATMs) impact the development obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding their effects on ATMs is limited. Here, we have shown that human mouse express NPFFR2, a receptor for appetite-reducing neuropeptide FF (NPFF), NPFFR2 expression upregulated by IL-4, an M2-polarizing cytokine. Plasma levels NPFF decreased obese patients high-fat diet-fed mice...
Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion controlling apoptosis, as studied animal models cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes increasing levels sulfatide would prevent NOD mice. We examined amount distribution pancreatic islets immunohistochemistry, immunofluorescence electron microscopy. Transcriptional analysis was used evaluate...
Abstract Loss of pancreatic beta cells is a central feature type 1 (T1D) and 2 (T2D) diabetes, but therapeutic strategy to preserve cell mass remains be established. Here we show that the death receptor TMEM219 expressed on signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads loss dysfunction. Increased peripheral IGFBP3 was observed in established at-risk T1D/T2D patients confirmed preclinical models, suggesting dysfunctional IGFBP3/TMEM219 associated...
Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of the heart and systemic organs. It remains uncertain whether peripheral blood mononuclear cells (PBMCs) are activated before tissue invasion by monocytes/macrophages lymphocytes, as is case for responsible pathogenic mechanisms. Uninephrectomized rats treated 4 weeks with dietary 1% NaCl aldosterone (ALDOST, 0.75 microg/h) or without spironolactone (Spi, 100 mg/kg per daily gavage) were compared...
Chronic inappropriate (relative to dietary Na + intake) elevations in circulating aldosterone (ALDO), termed aldosteronism, are associated with remodeling of intramural arteries the right and left heart. Lesions appear at week 4 treatment ALDO 1% NaCl uninephrectomized rats (ALDOST) include invading monocytes, macrophages lymphocytes intracellular evidence oxidative nitrosative stress, myofibroblasts, perivascular fibrosis. In this study, we tested hypothesis that an immunostimulatory state...
Congestive heart failure (CHF) is a clinical syndrome with origins rooted in salt-avid state largely mediated by effector hormones of the circulating renin-angiotensin-aldosterone system. Other participating neurohormones include catecholamines, endothelin-1, and arginine vasopressin. CHF accompanied systemic illness uncertain causality. Features appearance oxidative/nitrosative stress wasting tissues including bone. Herein we hypothesized that inappropriate (relative to dietary Na+)...
Background— Chronic, inappropriate (relative to dietary Na + ) elevations in circulating aldosterone, such as occur congestive heart failure, are accompanied by a proinflammatory vascular phenotype involving the coronary and systemic vasculature. An immunostimulatory state with activated peripheral blood mononuclear cells (PBMCs) precedes this is induced fall cytosolic free [Mg 2+ ] i subsequent Ca loading of these transduced oxidative/nitrosative stress. Methods Results— We sought further...
O-Glycosylation and phosphorylation of Sp1 are thought to modulate the expression a number genes in normal diabetic state. is an obligatory transcription factor for constitutive insulin-responsive calmodulin gene (Majumdar, G., Harmon, A., Candelaria, R., Martinez-Hernandez, Raghow, Solomon, S. (2003) Am. J. Physiol. 285, E584-E591). Here we report temporal dynamics accumulation total, O-GlcNAc-modified, phosphorylated H-411E hepatoma cells by immunohistochemistry with monospecific...
The hypercalciuria and hypermagnesuria that accompany aldosteronism contribute to a fall in plasma ionized extracellular Ca2+ Mg2+ concentrations ([Ca2+]o [Mg2+]o). Despite these losses the decline levels of cations, total intracellular cytosolic free concentration ([Ca2+]i) is increased oxidative stress induced. This involves diverse tissues, including peripheral blood mononuclear cells (PBMC) plasma. accompanying elevation parathyroid hormone (PTH) reduction bone mineral density caused by...
Abstract l-Arginine (l-Arg) is an insulin secretagogue, but the molecular mechanism whereby it stimulates secretion from β-cells not known. The possibility that l-Arg regulates through a G protein-coupled receptor (GPCR)-mediated suggested by high expression of nutrient GPCR family C group 6 member A (GPRC6A) in pancreas and TC-6 finding Gprc6a−/]minus] mice have abnormalities glucose homeostasis. To test direct role GPRC6A regulating secretion, we evaluated response pancreatic islets...
We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human antigens characterized their identity.Sera were collected participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to Health ABC enriched general population. The resulting sample (mean age: 79.2±3.9 years old) included early advanced AMD (n = 131) controls 231). Sera tested by Western blots...
A single injection of syngeneic islet cells into the thymus 4-week-old NOD/Lt female mice strongly retards diabetogenesis. The present study used intrathymic route antigen administration to compare relative efficacy peptides/proteins derived from two major candidate pancreatic β-cell autoantigens, insulin and GAD65, modulate Intrathymic B chain or recombinant human GAD65 significantly suppressed diabetogenesis during a 20-week follow-up period, whereas no protection was mediated by either...