A5068362253- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Pharmacology and Obesity Treatment
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Diabetes Management and Research
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Bariatric Surgery and Outcomes
- Diabetes and associated disorders
- Asthma and respiratory diseases
- Cardiovascular Disease and Adiposity
- Receptor Mechanisms and Signaling
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Diet, Metabolism, and Disease
- Cardiovascular Function and Risk Factors
- Neurotransmitter Receptor Influence on Behavior
- Adipokines, Inflammation, and Metabolic Diseases
- Eosinophilic Esophagitis
- Obesity and Health Practices
- IL-33, ST2, and ILC Pathways
- Pulmonary Hypertension Research and Treatments
- Liver Disease Diagnosis and Treatment
- Neuropeptides and Animal Physiology
- Body Composition Measurement Techniques
VA Tennessee Valley Healthcare System
2016-2025
Vanderbilt University Medical Center
2016-2025
Vanderbilt University
2014-2024
Diabetes Australia
2019
United States Department of Veterans Affairs
2013
Medical University of South Carolina
1999
University of Colorado Health
1990
The activation of many tyrosine kinases leads to the phosphorylation and phospholipase C-γ1 (PLC-γ1). To examine biological function this protein, homologous recombination has been used selectively disrupt Plcg1 gene in mice. Homozygous disruption results embryonic lethality at approximately day (E) 9.0. Histological analysis indicates that (−/−) embryos appear normal E 8.5 but fail continue development growth beyond 8.5–E9.0. These clearly demonstrate PLC-γ1 with, by inference, its capacity...
Summary To determine the application limits of green fluorescent protein (GFP) as a reporter gene or tag, we expressed GFP by itself and with fusion partners, used three different imaging methods to identify fluorescence. In conventional epifluorescence photomicroscopy, in cells could be distinguished bright signal over yellow‐green autofluorescence background. quantitative fluorescence microscopy, however, is contaminated cellular autofluorescence. Improved separation from HeLa cell was...
ABSTRACT Correct development of the limb is dependent on coordination between three distinct signaling centers. Recently, fibroblast growth factor-4 has been identified as a crucial determinant AER function, which directs bud outgrowth, and Sonic hedgehog molecule that mediates ZPA specifies anterior-posterior patterning in developing bud. In addition, Shh FGF-4 reciprocally reinforce each other’s expression via positive feedback loop, providing molecular basis for outgrowth patterning. The...
Patients with pulmonary arterial hypertension have increased prevalence of insulin resistance. We aimed to determine whether metabolic defects are associated bone morphogenic protein receptor type 2 (Bmpr2) mutations in mice, and these may contribute vascular disease development. Metabolic phenotyping was performed on transgenic mice inducible expression Bmpr2 mutation, R899X. Phenotypic penetrance R899X assessed a high-fat diet model Alterations glucocorticoid responses were murine...
Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not acidosis and, therefore, may lead faster resolution DKA than saline.To compare clinical effects balanced crystalloids with saline acute treatment adults DKA.This study was a subgroup analysis in 2 previously reported companion trials-Saline Against Lactated Ringer's or...
Pulmonary arterial hypertension (PAH) is a deadly disease of the small pulmonary vasculature with an increased prevalence insulin resistance (IR). Insulin regulates both glucose and lipid homeostasis. We sought to quantify glucose- lipid-related IR in human PAH, testing hypothesis that lipoprotein indices are more sensitive PAH.Oral tolerance PAH patients triglyceride-matched (TG-matched) controls proteomic, metabolomics, analyses were performed controls. Results validated external cohort...
To investigate the hypothesis that weight loss with glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in proportion of fat lean tissue mass when compared caloric restriction (CR) alone, as well treatment sitagliptin, dipeptidyl peptidase-4 (DPP-4) inhibitor, also enhances GLP-1 activity - determine independent effects each treatment.
Abstract —The minK gene encodes a 129-amino acid peptide the expression of which modulates function cardiac delayed rectifier currents ( I Kr and Ks ), mutations in are now recognized as one cause congenital long-QT syndrome. We have generated minK- deficient mice bacterial lacZ has been substituted for coding region such that β-galactosidase is controlled by endogenous regulatory elements. In myocytes isolated from wild-type neonatal mice, rarely recorded, while common. (–/–) myocytes,...
The prevalence of obesity has increased dramatically worldwide. epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment central kinase (Akt) involved in insulin signaling induced by exposure to high-fat (HF) diet dysregulation higher order circuitry feeding. Dopamine (DA) rich brain structures, such as striatum, provide motivation stimuli In these circuitries, DA dysfunction is posited...
We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus (T2DM) treated liraglutide versus comparator therapies.Twenty-six-week data from seven phase 3, randomized trials T2DM development programme were analysed by trial treatment group: (1.2 1.8 mg), active placebo. Outcome measures included proportions of various categories their percentage baseline; impact body mass index (BMI) gastrointestinal (GI) adverse events (AEs) on...
The mammalian target of rapamycin (mTOR) complex 2 (mTORC2) is a multimeric signaling unit that phosphorylates protein kinase B/Akt following hormonal and growth factor stimulation. Defective Akt phosphorylation at the mTORC2-catalyzed Ser473 site has been linked to schizophrenia. While human imaging animal studies implicate fundamental role for in prefrontal dopaminergic networks, molecular mechanisms linking specific schizophrenia-related neurotransmission abnormalities have not yet...
Background Metabolic dysfunction is highly prevalent in pulmonary arterial hypertension (PAH) and likely contributes to both vascular disease right ventricular (RV) failure part because of increased oxidant stress. Currently, there no cure for PAH human studies metabolic interventions, generally well tolerated other diseases, are limited PAH. Metformin a commonly used oral antidiabetic that decreases gluconeogenesis, increases fatty acid oxidation, reduces stress thus may be relevant Methods...
Obesity is a risk factor for the development of asthma. However, pharmacologic therapeutic strategies that specifically target obese asthmatics have not been identified. We hypothesize glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment inhibits aeroallergen-induced early innate airway inflammation in mouse model asthma setting obesity.SWR (lean) and TALLYHO (obese) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or PBS 4 consecutive days concurrent...
Reducing dietary energy density has proven to be an effective strategy reduce intakes and promote weight control. This effect appears most robust when a low dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of preload. The purpose present study was compare effects solid (grapefruit), liquid (grapefruit juice) water prior breakfast, lunch dinner in context caloric restriction.Eighty-five obese adults (BMI 30-39.9) were randomly assigned (127 g)...
Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of mTORC2 complex required for hydrophobic motif site phosphorylation Akt at serine 473. To examine contribution neuronal Rictor/mTORC2 to CNS regulation homeostasis, we utilized Cre-LoxP technology generate mice lacking all neurons, or either POMC AgRP expressing neurons. deletion neurons led increased fat mass adiposity,...
Vascular health factors frequently co-occur with Alzheimer's disease (AD). A better understanding of how systemic vascular and cerebrovascular intersects clinical pathological AD may inform prevention treatment opportunities.To establish the Vanderbilt Memory & Aging Project, a case-control longitudinal study investigating brain aging, describe baseline methodology participant characteristics.From September 2012 to November 2014, 335 participants age 60- 92 were enrolled, including 168...