A5031618666- Alzheimer's disease research and treatments
- Pancreatic function and diabetes
- Neurological Disease Mechanisms and Treatments
- Dementia and Cognitive Impairment Research
- Protein Structure and Dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Chemical Physics Studies
- Advanced Glycation End Products research
- Neurological Disorders and Treatments
- Cardiovascular Function and Risk Factors
- Microbial Inactivation Methods
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- nanoparticles nucleation surface interactions
- Lipid Membrane Structure and Behavior
- Diabetes Treatment and Management
- Proteins in Food Systems
- Eicosanoids and Hypertension Pharmacology
- Atomic and Molecular Physics
- Advanced Thermodynamics and Statistical Mechanics
- Cardiac electrophysiology and arrhythmias
- Theoretical and Computational Physics
- Parkinson's Disease Mechanisms and Treatments
- Bacillus and Francisella bacterial research
University of Kentucky
2016-2025
University of Kentucky HealthCare
2017
University of California, Davis
2008-2013
University of Pennsylvania
2012
University of Chicago
2001-2009
KU Leuven
1999-2001
Institutul de Fizică Atomică
1995-1999
Institute of Atomic Energy
1996
The Abdus Salam International Centre for Theoretical Physics (ICTP)
1994-1996
National Institute of Materials Physics
1995
Hyperamylinemia, a common pancreatic disorder in obese and insulin-resistant patients, is known to cause amylin oligomerization cytotoxicity islets, leading β-cell mass depletion development of type 2 diabetes. Recent data has revealed that hyperamylinemia also affects the vascular system, heart, kidneys. We therefore hypothesized oligomerized might accumulate cerebrovascular system brain parenchyma diabetic patients.Amylin accumulation patients with dementia or Alzheimer disease (AD),...
We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized co-secreted insulin by pancreatic β-cells. Amylin deposition is promoted chronic hypersecretion amylin (hyperamylinemia), which common in humans obesity or pre-diabetic resistance. Human oligomerizes quickly when oversecreted, toxic, induces inflammation islets contributes to the development T2D. Here, we tested hypothesis...
Rationale: Hyperamylinemia is common in patients with obesity and insulin resistance, coincides hyperinsulinemia, results amyloid deposition. Amylin amyloids are generally considered a pancreatic disorder type 2 diabetes. However, elevated circulating levels of amylin may also lead to accumulation proteotoxicity peripheral organs, including the heart. Objective: To test whether accumulates heart obese diabetic uncover effects on cardiac morphology function. Methods Results: We compared...
Intracellular Na(+) concentration ([Na(+)]i) regulates Ca(2+) cycling, contractility, metabolism, and electrical stability of the heart. [Na(+)]i is elevated in heart failure, leading to arrhythmias oxidative stress. We hypothesized that myocyte also increased type 2 diabetes (T2D) due enhanced activity Na(+)-glucose cotransporter.To test this hypothesis, we used myocardial tissue from humans with T2D a rat model late-onset (HIP rat). Western blot analysis showed cotransporter expression...
A new dual-target dual-laser vaporization source for the production of binary metallic clusters is presented. Clusters type AunXm (X=Al, Fe, Co, Ni) were produced. Excellent control over mixing process was achieved by varying delay time between firing two lasers and their energy densities. Having identified these critical parameters, influence shown in detail AunAlm system. The bimetallic this due to spatial temporal overlap laser vaporized materials source.
Abstract Hyperglycemia (HG) stimulates the production of reactive oxygen species in heart through activation NADPH oxidase 2 (NOX2). This is independent glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression function remain elusive. We investigated these 7 found that only SGLT1 SMIT1 were expressed mouse, rat human hearts. In cardiomyocytes, galactose...
The brain blood vessels of patients with type 2 diabetes and dementia have deposition amylin, an amyloidogenic hormone cosecreted insulin. It is not known whether vascular amylin a consequence or trigger injury. We tested the hypothesis that deposits cause endothelial dysfunction microvascular injury are modulated by transport in via plasma apolipoproteins.Rats overexpressing (human) pancreas (HIP rats) knockout (AKO) rats intravenously infused aggregated were used for vivo phenotyping. also...
Amylin is a hormone synthesized and co-secreted with insulin by pancreatic β-cells that crosses the blood-brain barrier regulates satiety. from humans (but not rodents) has an increased propensity to aggregate into islet amyloid deposits contribute β-cell mass depletio n development of type-2 diabetes inducing oxidative stress inflammation. Recent studies demonstrated aggregated amylin also accumulates in brains Alzheimer's disease (AD) patients, preponderantly those diabetes. Here, we...
Introduction: Type-2 diabetes increases the risk of stroke; however, mechanisms remain incompletely understood. Using a rat model type-2 that expresses amyloid-forming human amylin in pancreas (the HIP rat), we previously reported deposits brain microvasculature causing microhemorrhages and neurological deficits. Here, tested hypotheses: 1, amylin-mediated cerebral microvascular injury involve damage endothelial cell tight junctions; 2, an increase epoxyeicosatrienoic acids (EETs),...
We show that water constrained by vicinal hydrophobes undergoes a librational dynamics lowers the dielectric susceptibility and induces ``redshift'' of relaxation frequency in hydration shell. The results shed light on way proteins enhance their intramolecular interactions as they fold or associate.
Background Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces aggregation proteotoxicity pancreas. We recently showed that hyperamylinemia also affects cardiovascular system. Here, we investigated whether aggregates interact directly cardiac myocytes controlling protects heart. Methods Results By Western blot, found abundant lysates from obese patients, but not controls. Aggregated was elevated failing...
Abstract Impairment of vascular pathways cerebral β-amyloid (Aβ) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs Aβ clearance. Blood amylin concentrations are higher AD than cognitively unaffected persons. Amyloid-forming accumulates circulating monocytes co-deposits within brain microvasculature,...
Abstract Introduction This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD). Methods Evidence of amylin‐AD pathology interaction was tested brains 31 familial AD mutation carriers and 20 cognitively unaffected individuals, cerebrospinal fluid (CSF) (98 diseased 117 control samples) genetic databases. For functional testing, we genetically manipulated secretion APP/PS1 non‐APP/PS1 rats. Results...
Hypersecretion of amylin is common in individuals with prediabetes, causes deposition and proteotoxicity pancreatic islets, contributes to the development type 2 diabetes. Recent studies also identified deposits failing hearts from patients obesity or diabetes demonstrated that hyperamylinemia accelerates heart dysfunction rats expressing human β-cells (HIP rats). To further determine impact on cardiac myocytes, we investigated myocardium, compared diabetic HIP endogenous (nonamyloidogenic)...
Bridging integrator 1 (BIN1) is the most significant late-onset Alzheimer's disease (AD) susceptibility locus identified via genome-wide association studies. BIN1 an adaptor protein that regulates membrane dynamics in context of endocytosis and remodeling. An increase expression changes relative levels alternatively spliced isoforms have been reported brains patients with AD. can bind to Tau, correlates Tau pathology. In contrast, loss cultured cells elevates Aβ production propagation by...