A5025336530- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Diabetes Management and Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Clinical Nutrition and Gastroenterology
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Liver Disease Diagnosis and Treatment
- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Receptor Mechanisms and Signaling
- Dietary Effects on Health
- Muscle metabolism and nutrition
- Growth Hormone and Insulin-like Growth Factors
- Cardiovascular and exercise physiology
- Peroxisome Proliferator-Activated Receptors
- Immune Response and Inflammation
- Diet, Metabolism, and Disease
- Metabolomics and Mass Spectrometry Studies
- Heart Rate Variability and Autonomic Control
- Cardiovascular Function and Risk Factors
- Fibroblast Growth Factor Research
- Circadian rhythm and melatonin
Vanderbilt University
2016-2025
Vanderbilt University Medical Center
1991-2024
University of California, San Diego
2024
Nashville Oncology Associates
2019
Yeshiva University
2015
Institute of Molecular Biology and Biophysics
2014
Physiol (Belgium)
2008
National Institute of Diabetes and Digestive and Kidney Diseases
2006
The University of Texas Southwestern Medical Center
2005
Southwestern Medical Center
2005
A defect in Klotho gene expression mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression extends life span. protein functions as a circulating hormone binds to cell-surface receptor and represses intracellular signals insulin insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending Alleviation aging-like phenotypes Klotho-deficient was observed by perturbing IGF1 signaling, suggesting Klotho-mediated inhibition...
The Mouse Metabolic Phenotyping Center (MMPC) Consortium was established to address the need characterize growing number of mouse models metabolic diseases, particularly diabetes and obesity. A goal MMPC is propose standard methods for assessing phenotypes in mice. In this article, we discuss issues pertaining design performance various tests glucose metabolism. We also guidelines description methods, presentation data interpretation results. recommendations presented article are based on...
Despite increased use of the hyperinsulinemic-euglycemic clamp to study insulin action in mice, effects experimental parameters on results obtained have not been addressed. In our studies, we determined influences sampling sites, fasting duration, and delivery from clamps conscious mice. Carotid artery jugular vein catheters were implanted C57BL/6J mice (n = 6–10/group) fed a normal diet for infusions. After 5-day recovery period, underwent 120-min (2.5-mU · kg−1 min−1 infusion; ∼120–130...
Increased plasminogen activator inhibitor 1 (PAI-1) has been linked to not only thrombosis and fibrosis but also obesity insulin resistance. PAI-1 levels have presumed be consequent obesity. We investigated the interrelationships of PAI-1, obesity, resistance in a high-fat/high-carbohydrate (HF) diet–induced model wild-type (WT) PAI-1–deficient mice (PAI-1−/−). Obesity developing WT on an HF diet were completely prevented lacking PAI-1. PAI-1−/− had increased resting metabolic rates total...
Pathway-selective insulin resistance where fails to suppress hepatic glucose production but promotes liver fat storage may underlie and lipid abnormalities after menopause. We tested the mechanisms by which estrogen treatment alter impact of a high-fat diet (HFD) when given at time ovariectomy (OVX) in mice. Female C57BL/6J mice underwent sham operation, OVX, or OVX with estradiol (E2) were fed an HFD. Hyperinsulinemic-euglycemic clamps used assess sensitivity, tracer incorporation into...
Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual development these disorders; therefore, altering person’s may ameliorate disease. One potential microbiome-altering strategy incorporation modified bacteria that express therapeutic factors into gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) precursors...
Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It not clear if adropin hormone regulated by signals of metabolic state. Moreover, the significance decline in expression with obesity respect disease also clear. We investigated regulation serum status diet. Serum levels were high chow-fed conditions suppressed fasting (DIO). High observed mice fed high-fat low carbohydrate diet, whereas lower low-fat To...
Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity function within multicellular tissues through incompletely known mechanisms. By assembling a atlas of chromatin state human islets, we identified β cell subtypes governed by either high or low activity the factor pancreatic duodenal homeobox-1 (PDX1). cells with reduced PDX1 displayed increased accessibility at latent nuclear κB (NF-κB) enhancers. Pdx1 hypomorphic mice...
Obesity is commonly associated with development of insulin resistance and systemic evidence inflammation. Macrophages contribute to inflammatory amplification in obesity may directly the nonalcoholic fatty liver disease through production cytokines, including tumor necrosis factor (TNF)-alpha. To test this hypothesis, we transplanted male wild-type (WT) TNF-alpha deficient (KO) mice either TNF-alpha-sufficient (TNF-alpha(+/+)) or TNF-alpha-deficient (TNF-alpha(-/-)) bone marrow. After...
Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis brown tissues; both contribute to incidences of obesity type 2 diabetes. Ghrelin the only known circulating orexigenic hormone that promotes adiposity. In this study, we show ablation ghrelin receptor (growth secretagogue receptor, GHS-R) improves insulin sensitivity during aging. Compared wild-type (WT) mice, old Ghsr(-/-) mice have reduced fat preserve a healthier lipid profile. Old also...
The Slc30a8 gene encodes the islet-specific zinc transporter ZnT-8, which provides for insulin-hexamer formation. Polymorphic variants in amino acid residue 325 of human ZnT-8 are associated with altered susceptibility to Type 2 diabetes and autoantibody epitope specificity changes 1 diabetes. To assess physiological importance mice carrying a exon 3 deletion were analysed histologically phenotyped energy metabolism pancreatic hormone secretion. No gross anatomical or behavioural differences...
The microRNA-29 (miR-29) family is among the most abundantly expressed microRNA in pancreas and liver. Here, we investigated function of miR-29 glucose regulation using miR-29a/b-1 (miR-29a)-deficient mice newly generated miR-29b-2/c (miR-29c)-deficient mice. We observed multiple independent functions family, which can be segregated into a hierarchical physiologic handling. miR-29a, not miR-29c, was to positive regulator insulin secretion vivo, with dysregulation exocytotic machinery...
AMP-activated protein kinase (AMPK) has been postulated as a super-metabolic regulator, thought to exert numerous effects on skeletal muscle function, metabolism, and enzymatic signaling. Despite these assertions, little is known regarding the direct role(s) of AMPK in vivo, results obtained vitro or situ are conflicting. Using chronically catheterized mouse model (carotid artery jugular vein), we show that regulates metabolism vivo at several levels, with result deficit activity markedly...
Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or widely considered the "gold standard" method for assessing action vivo. During an hyperinsulinemia achieved constant infusion. Euglycemia maintained via concomitant glucose infusion at variable rate. This rate (GIR) determined measuring blood brief intervals throughout experiment and adjusting GIR accordingly. indicative of whole-body action, as mice with enhanced require greater GIR....
The ability of skeletal muscle to enhance lipid utilization during exercise is a form metabolic plasticity essential for survival. Conversely, inflexibility in can cause organ dysfunction and disease. Although the transcription factor Kruppel-like 15 (KLF15) an important regulator glucose amino acid metabolism, its endogenous role homeostasis physiology unknown. Here we demonstrate that KLF15 physiologic performance. directly regulates broad transcriptional program spanning all major...
Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed a potential treatment for obesity-linked disorders. Here, we describe the generation humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, common FGF21 and FGF19. Using this molecule, show antibody-mediated activation FGFR1/βKlotho complex in mice induces sustained energy expenditure BAT, browning white tissue,...
To examine the relationship between net hepatic glucose uptake (NHGU) and insulin level to determine effects of portal delivery on that relationship, NHGU was evaluated at three different levels in seven 42-h-fasted, conscious dogs during peripheral a combination delivery. During delivery, arterial blood approximately 175 mg/dl reaching liver 51 +/- 2, 92 6, 191 6 microU/ml, respectively, NHGUs were 0.55 0.30, 1.52 0.44, 3.04 0.79 mg/kg per min, respectively. At loads comparable those...
Poly(ADP-ribose)polymerase (PARP)14—a member of the B aggressive lymphoma (BAL) family macrodomain-containing PARPs—is an ADP ribosyltransferase that interacts with Stat6, enhances induction certain genes by IL-4, and is expressed in lymphocytes. We now show IL-4 enhancement glycolysis cells requires PARP14 this process central to a role IL-4–induced survival. Thus, enhancements AMP-activated protein kinase activity restored both glycolytic Parp14 −/− prosurvival signaling cytokine....